Arthur Horwich, MD
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Research Summary
We are focused on misfolding-induced neurodegeneration caused by mutant forms of the cytosolic enzyme superoxide dismutase (SOD1), which produce a dominant-inherited form of ALS (Lou Gehrig’s Disease) with progressive motor neuron dysfunction that leads to lethal paralysis. Mutant SOD1-linked ALS accounts for ~2% of all ALS cases and ~20% of genetically-associated ALS. Notably, inherited and non-inherited forms of ALS in humans are indistinguishable at a clinical level. We are using mice overexpressing a mutant G85R SOD1-YFP fusion protein to study the mechanism of disease causation. The mouse model studied affords one of the most powerful approaches to following the development of this so far non-treatable neurodegenerative condition. The hope is that basic understanding may lead to directed therapy.
Extensive Research Description
Studies of the past decades have shown that many diseases of neurodegeneration are associated with protein misfolding and aggregation of specific proteins in particular neurons or glia, and we have been studying one such mechanism of degeneration. We have focused on misfolding/aggregation caused by mutant forms of the anti-oxidant cytosolic enzyme SOD1 (superoxide dismutase), which produces dominant-inherited ALS, with progressive paralyzing motor neuron dysfunction. We are using mice overexpressing mutant G85R SOD1-YFP, containing a mutant version of SOD1 unable to reach the native state, studying the transgenic animals with a variety of approaches to investigate how the mutant SOD1 produces motor dysfunction.
We have identified that there is a progression of misbehavior of mutant SOD1 protein itself in the spinal cord motor neurons of transgenic animals. Initially it is soluble and associated to a significant extent with the abundant cytosolic chaperone Hsc70 (by contrast to the wild-type protein, which does not form such association, presumably because it occupies the native homodimeric state). Subsequently, the mutant SOD1 proteiin begins to form both soluble oligomers (observable by gel filtration chromatography) and insoluble aggregates, and at this point an additional molecular chaperone, Hsp110, becomes associated with the soluble aggregates. A portion of the aggregates becomes insoluble and forms large structures in the cytosol of motor neurons. These cells become surrounded by microglia and appear to be subsequently removed. Associated with such loss, the affected animal initially exhibits mild lower extremity symptoms (weakness or pulling in when held by the tail at ~ 3 months of age), which progresses over the next 3-4 months to paralysis, usually commencing in the lower extremities.
We have used laser capture microdissection of motor neurons and RNA-seq from animals at mid-course to inspect for changes in transcriptional expression, but find only a small number of differences relative to the motor neurons from wild-type SOD1-YFP mice. Notably, there is no classical heat shock response beyond induction of Hsp110 and no ER unfolded protein response, but there are effects on several calcium binding proteins. We surmised that most of the toxicity of mutant SOD1 is exerted post-translationally. In collaboration with David McCormick’s group we carred out electrophysiologic measurements of motor neurons by patch clamping them in spinal cord of wild-type and mutant SOD1 mice in novel rapidly prepared slice preparations. This identified that the fast-firing motor neurons, which innervate fast twitch muscle, are the first to be lost. This observation was confirmed by studying wild-type or mutant mice running on a wheel while simultaneously monitoring single motor neurons in the ventral horn of the spinal cord by field potential measurements and the firing of corresponding lower extremity muscles. Most recently we have been screening a number of candidate genes for prolongation of the survival of the mutant ALS mice.
Research Interests
Amyotrophic Lateral Sclerosis; Genetics; Motor Neurons; Neurosciences; Pediatrics; Superoxide Dismutase; Protein Folding; Neurodegenerative Diseases
Selected Publications
- NMR analysis of a 900K GroEL–GroES complexFiaux J, Bertelsen E, Horwich A, Wüthrich K. NMR analysis of a 900K GroEL–GroES complex. 2021, 67-71. DOI: 10.1142/9789811235795_0007.
- Direct NMR observation of a substrate protein bound to the chaperonin GroELHorst R, Bertelsen E, Fiaux J, Wider G, Horwich A, Wüthrich K. Direct NMR observation of a substrate protein bound to the chaperonin GroEL. 2021, 99-104. DOI: 10.1142/9789811235795_0011.
- Chaperonin-assisted protein folding: a chronologueHorwich AL, Fenton WA. Chaperonin-assisted protein folding: a chronologue. Quarterly Reviews Of Biophysics 2020, 53: e4. PMID: 32070442, DOI: 10.1017/s0033583519000143.
- Hsp110 mitigates α-synuclein pathology in vivoTaguchi YV, Gorenberg EL, Nagy M, Thrasher D, Fenton WA, Volpicelli-Daley L, Horwich AL, Chandra SS. Hsp110 mitigates α-synuclein pathology in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24310-24316. PMID: 31685606, PMCID: PMC6883785, DOI: 10.1073/pnas.1903268116.
- Transfer of pathogenic and nonpathogenic cytosolic proteins between spinal cord motor neurons in vivo in chimeric miceThomas EV, Fenton WA, McGrath J, Horwich AL. Transfer of pathogenic and nonpathogenic cytosolic proteins between spinal cord motor neurons in vivo in chimeric mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e3139-e3148. PMID: 28348221, PMCID: PMC5393223, DOI: 10.1073/pnas.1701465114.
- Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS miceHadzipasic M, Ni W, Nagy M, Steenrod N, McGinley MJ, Kaushal A, Thomas E, McCormick DA, Horwich AL. Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e7600-e7609. PMID: 27821773, PMCID: PMC5127366, DOI: 10.1073/pnas.1616832113.
- Structure and Action of Molecular ChaperonesGierasch L, Horwich A, Slingsby C, Wickner S, Agard D. Structure and Action of Molecular Chaperones. 2015, 6 DOI: 10.1142/9927.
- Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALSHadzipasic M, Tahvildari B, Nagy M, Bian M, Horwich AL, McCormick DA. Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALS. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16883-16888. PMID: 25385594, PMCID: PMC4250117, DOI: 10.1073/pnas.1419497111.
- 3.10 Chaperones and Protein FoldingHorwich A, Buchner J, Smock R, Gierasch L, Saibil H. 3.10 Chaperones and Protein Folding. 2012, 212-237. DOI: 10.1016/b978-0-12-374920-8.00313-1.
- The GroEL/GroES Chaperonin MachineHorwich A, Saibil H. The GroEL/GroES Chaperonin Machine. 2011, 191-207. DOI: 10.1017/cbo9781139003704.012.
- GroEL/GroES‐mediated protein foldingHorwich A, Tyagi N, Clare D, Saibil H. GroEL/GroES‐mediated protein folding. The FASEB Journal 2011, 25: 319.3-319.3. DOI: 10.1096/fasebj.25.1_supplement.319.3.
- GroEL‐GroES‐mediated protein foldingHorwich A, Chapman E, Koculi E, Apetri A, Fenton W, Farr G, Horst R, Wüthrich K. GroEL‐GroES‐mediated protein folding. The FASEB Journal 2008, 22: 536.2-536.2. DOI: 10.1096/fasebj.22.1_supplement.536.2.
- GroEL—GroES‐Mediated Protein FoldingHorwich A, Farr G, Fenton W. GroEL—GroES‐Mediated Protein Folding. ChemInform 2006, 37: no-no. DOI: 10.1002/chin.200631298.
- ChaperoninsHorwich A, Fenton W, Farr G. Chaperonins. 2004, 393-398. DOI: 10.1016/b0-12-443710-9/00102-2.
- The Role of ATP in directing chaperonin-mediated polypeptide foldingHorwich A, Fenton W. The Role of ATP in directing chaperonin-mediated polypeptide folding. 2003, 23: 399-xii. DOI: 10.1016/s1874-6047(04)80010-6.
- ATP-bound states of GroEL and GroEL-GroES captured by cryo-EM and single particle image processingRanson N, Farr G, Roseman A, Gowen B, Fenton W, Horwich A, Saibil H. ATP-bound states of GroEL and GroEL-GroES captured by cryo-EM and single particle image processing. Acta Crystallographica Section A: Foundations And Advances 2002, 58: c7-c7. DOI: 10.1107/s0108767302085367.
- Protein folding taking shapeHorwich A, Fenton W, Rapoport T. Protein folding taking shape. EMBO Reports 2001, 2: 1068-1073. PMID: 11743017, PMCID: PMC1084171, DOI: 10.1093/embo-reports/kve253.
- ATP-Bound States of GroEL Captured by Cryo-Electron MicroscopyRanson N, Farr G, Roseman A, Gowen B, Fenton W, Horwich A, Saibil H. ATP-Bound States of GroEL Captured by Cryo-Electron Microscopy. Cell 2001, 107: 869-879. PMID: 11779463, DOI: 10.1016/s0092-8674(01)00617-1.
- GroEL/GroES-Mediated Folding of a Protein Too Large to Be EncapsulatedChaudhuri T, Farr G, Fenton W, Rospert S, Horwich A. GroEL/GroES-Mediated Folding of a Protein Too Large to Be Encapsulated. Cell 2001, 107: 235-246. PMID: 11672530, DOI: 10.1016/s0092-8674(01)00523-2.
- Folding of malate dehydrogenase inside the GroEL–GroES cavityChen J, Walter S, Horwich A, Smith D. Folding of malate dehydrogenase inside the GroEL–GroES cavity. Nature Structural & Molecular Biology 2001, 8: 721-728. PMID: 11473265, DOI: 10.1038/90443.
- ClpA mediates directional translocation of substrate proteins into the ClpP proteaseReid B, Fenton W, Horwich A, Weber-Ban E. ClpA mediates directional translocation of substrate proteins into the ClpP protease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 3768-3772. PMID: 11259663, PMCID: PMC31127, DOI: 10.1073/pnas.071043698.
- Mechanisms of protein foldingGrantcharova V, Alm E, Baker D, Horwich A. Mechanisms of protein folding. Current Opinion In Structural Biology 2001, 11: 70-82. PMID: 11179895, DOI: 10.1016/s0959-440x(00)00176-7.
- Allostery and protein substrate conformational change during GroEL/GroES-mediated protein foldingSaibil H, Horwich A, Fenton W. Allostery and protein substrate conformational change during GroEL/GroES-mediated protein folding. 2001, 59: 45-72. PMID: 11868280, DOI: 10.1016/s0065-3233(01)59002-6.
- Multivalent Binding of Nonnative Substrate Proteins by the Chaperonin GroELFarr G, Furtak K, Rowland M, Ranson N, Saibil H, Kirchhausen T, Horwich A. Multivalent Binding of Nonnative Substrate Proteins by the Chaperonin GroEL. Cell 2000, 100: 561-573. PMID: 10721993, DOI: 10.1016/s0092-8674(00)80692-3.
- Chaperone rings in protein folding and degradationHorwich A, Weber-Ban E, Finley D. Chaperone rings in protein folding and degradation. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 11033-11040. PMID: 10500119, PMCID: PMC34237, DOI: 10.1073/pnas.96.20.11033.
- Global unfolding of a substrate protein by the Hsp100 chaperone ClpAWeber-Ban E, Reid B, Miranker A, Horwich A. Global unfolding of a substrate protein by the Hsp100 chaperone ClpA. Nature 1999, 401: 90-93. PMID: 10485712, DOI: 10.1038/43481.
- GroEL-GroES Cycling ATP and Nonnative Polypeptide Direct Alternation of Folding-Active RingsRye H, Roseman A, Chen S, Furtak K, Fenton W, Saibil H, Horwich A. GroEL-GroES Cycling ATP and Nonnative Polypeptide Direct Alternation of Folding-Active Rings. Cell 1999, 97: 325-338. PMID: 10319813, DOI: 10.1016/s0092-8674(00)80742-4.
- Maturation of Human Cyclin E Requires the Function of Eukaryotic Chaperonin CCTWon K, Schumacher R, Farr G, Horwich A, Reed S. Maturation of Human Cyclin E Requires the Function of Eukaryotic Chaperonin CCT. Molecular And Cellular Biology 1998, 18: 7584-7589. PMID: 9819444, PMCID: PMC109339, DOI: 10.1128/mcb.18.12.7584.
- Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by the SSA class of cytosolic yeast Hsp70 proteinsKim S, Schilke B, Craig E, Horwich A. Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by the SSA class of cytosolic yeast Hsp70 proteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 12860-12865. PMID: 9789005, PMCID: PMC23633, DOI: 10.1073/pnas.95.22.12860.
- STRUCTURE AND FUNCTION IN GroEL-MEDIATED PROTEIN FOLDINGSigler P, Xu Z, Rye H, Burston S, Fenton W, Horwich A. STRUCTURE AND FUNCTION IN GroEL-MEDIATED PROTEIN FOLDING. Annual Review Of Biochemistry 1998, 67: 581-608. PMID: 9759498, DOI: 10.1146/annurev.biochem.67.1.581.
- The thermosome: chaperonin with a built-in lidHorwich A, Saibil H. The thermosome: chaperonin with a built-in lid. Nature Structural & Molecular Biology 1998, 5: 333-336. PMID: 9586988, DOI: 10.1038/nsb0598-333.
- The Hsp70 and Hsp60 Chaperone MachinesBukau B, Horwich A. The Hsp70 and Hsp60 Chaperone Machines. Cell 1998, 92: 351-366. PMID: 9476895, DOI: 10.1016/s0092-8674(00)80928-9.
- Chaperone Action in Folding Newly-Translated Cytosolic Proteins in Bacteria and EukaryotesHorwich A. Chaperone Action in Folding Newly-Translated Cytosolic Proteins in Bacteria and Eukaryotes. 1998, 41-63. DOI: 10.1007/978-3-642-51463-0_4.
- [11] Construction of single-ring and two-ring hybrid versions of bacterial chaperonin GroELHorwich A, Burston S, Rye H, Weissman J, Fenton W. [11] Construction of single-ring and two-ring hybrid versions of bacterial chaperonin GroEL. 1998, 290: 141-146. PMID: 9534157, DOI: 10.1016/s0076-6879(98)90013-1.
- The crystal structure of the asymmetric GroEL–GroES–(ADP)7 chaperonin complexXu Z, Horwich A, Sigler P. The crystal structure of the asymmetric GroEL–GroES–(ADP)7 chaperonin complex. Nature 1997, 388: 741-750. PMID: 9285585, DOI: 10.1038/41944.
- Distinct actions of cis and trans ATP within the double ring of the chaperonin GroELRye H, Burston S, Fenton W, Beechem J, Xu Z, Sigler P, Horwich A. Distinct actions of cis and trans ATP within the double ring of the chaperonin GroEL. Nature 1997, 388: 792-798. PMID: 9285593, DOI: 10.1038/42047.
- Chaperonin-Mediated Folding in the Eukaryotic Cytosol Proceeds through Rounds of Release of Native and Nonnative FormsFarr G, Scharl E, Schumacher R, Sondek S, Horwich A. Chaperonin-Mediated Folding in the Eukaryotic Cytosol Proceeds through Rounds of Release of Native and Nonnative Forms. Cell 1997, 89: 927-937. PMID: 9200611, DOI: 10.1016/s0092-8674(00)80278-0.
- Deadly Conformations—Protein Misfolding in Prion DiseaseHorwich A, Weissman J. Deadly Conformations—Protein Misfolding in Prion Disease. Cell 1997, 89: 499-510. PMID: 9160742, DOI: 10.1016/s0092-8674(00)80232-9.
- GroEL‐Mediated protein foldingFenton W, Horwich A. GroEL‐Mediated protein folding. Protein Science 1997, 6: 743-760. PMID: 9098884, PMCID: PMC2144759, DOI: 10.1002/pro.5560060401.
- Native-like structure of a protein-folding intermediate bound to the chaperonin GroELGoldberg M, Zhang J, Sondek S, Matthews C, Fox R, Horwich A. Native-like structure of a protein-folding intermediate bound to the chaperonin GroEL. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 1080-1085. PMID: 9037009, PMCID: PMC19747, DOI: 10.1073/pnas.94.4.1080.
- Putting a lid on protein folding: structure and function of the co-chaperonin, GroESFenton W, Weissman J, Horwich A. Putting a lid on protein folding: structure and function of the co-chaperonin, GroES. Cell Chemical Biology 1996, 3: 157-161. PMID: 8807841, DOI: 10.1016/s1074-5521(96)90257-4.
- Characterization of the Active Intermediate of a GroEL–GroES-Mediated Protein Folding ReactionWeissman J, Rye H, Fenton W, Beechem J, Horwich A. Characterization of the Active Intermediate of a GroEL–GroES-Mediated Protein Folding Reaction. Cell 1996, 84: 481-490. PMID: 8608602, DOI: 10.1016/s0092-8674(00)81293-3.
- 5 Structure and Function of Chaperonins in Archaebacteria and Eukaryotic CytosolWillison K, Horwich A. 5 Structure and Function of Chaperonins in Archaebacteria and Eukaryotic Cytosol. 1996, 107-136. DOI: 10.1016/b978-012237455-5/50006-3.
- Unliganded GroEL at 2.8 Å: structure and functional implicationsSigler P, Horwich A. Unliganded GroEL at 2.8 Å: structure and functional implications. Philosophical Transactions Of The Royal Society B Biological Sciences 1995, 348: 113-119. PMID: 7770481, DOI: 10.1098/rstb.1995.0052.
- From the Cradle to the Grave: Ring Complexes in the Life of a ProteinWeissman J, Sigler P, Horwich A. From the Cradle to the Grave: Ring Complexes in the Life of a Protein. Science 1995, 268: 523-524. PMID: 7725096, DOI: 10.1126/science.7725096.
- Kinesis of polypeptide during GroEL-mediated folding.Horwich A, Weissman J, Fenton W. Kinesis of polypeptide during GroEL-mediated folding. Cold Spring Harbor Symposia On Quantitative Biology 1995, 60: 435-40. PMID: 8824417, DOI: 10.1101/sqb.1995.060.01.048.
- Cystosolic chaperonin subunits have a conserved ATPase domain but diverged polypeptide-binding domainsKim S, Willison K, Horwich A. Cystosolic chaperonin subunits have a conserved ATPase domain but diverged polypeptide-binding domains. Trends In Biochemical Sciences 1994, 19: 543-548. PMID: 7846767, DOI: 10.1016/0968-0004(94)90058-2.
- A carboxy-terminal deletion impairs the assembly of GroEL and confers a pleiotropic phenotype in Escherichia coli K-12.Burnett B, Horwich A, Low K. A carboxy-terminal deletion impairs the assembly of GroEL and confers a pleiotropic phenotype in Escherichia coli K-12. Journal Of Bacteriology 1994, 176: 6980-6985. PMID: 7961461, PMCID: PMC197070, DOI: 10.1128/jb.176.22.6980-6985.1994.
- The crystal structure of the bacterial chaperonln GroEL at 2.8 ÅBraig K, Otwinowski Z, Hegde R, Boisvert D, Joachimiak A, Horwich A, Sigler P. The crystal structure of the bacterial chaperonln GroEL at 2.8 Å. Nature 1994, 371: 578-586. PMID: 7935790, DOI: 10.1038/371578a0.
- Heat shock proteins and molecular chaperones: Mediators of protein conformation and turnover in the cellCraig E, Weissman J, Horwich A. Heat shock proteins and molecular chaperones: Mediators of protein conformation and turnover in the cell. Cell 1994, 78: 365-372. PMID: 7914834, DOI: 10.1016/0092-8674(94)90416-2.
- GroEL-mediated protein folding proceeds by multiple rounds of binding and release of nonnative formsWeissman J, Kashi Y, Fenton W, Horwich A. GroEL-mediated protein folding proceeds by multiple rounds of binding and release of nonnative forms. Cell 1994, 78: 693-702. PMID: 7915201, DOI: 10.1016/0092-8674(94)90533-9.
- Short‐term response to dietary therapy in molybdenum cofactor deficiencyBoles R, Ment L, Meyn M, Horwich A, Kratz L, Rinaldo P. Short‐term response to dietary therapy in molybdenum cofactor deficiency. Annals Of Neurology 1993, 34: 742-744. PMID: 7694543, DOI: 10.1002/ana.410340520.
- Folding in vivo of bacterial cytoplasmic proteins: Role of GroELHorwich A, Low K, Fenton W, Hirshfield I, Furtak K. Folding in vivo of bacterial cytoplasmic proteins: Role of GroEL. Cell 1993, 74: 909-917. PMID: 8104102, DOI: 10.1016/0092-8674(93)90470-b.
- High-resolution gold labelingHainfeld J, Furuya F, Carbone K, Simon M, Lin B, Braig K, Horwich A, Safer D, Blechschmidt B, Sprinzl M, Ofengand J, Boublik M. High-resolution gold labeling. Microscopy And Microanalysis 1993, 51: 330-331. DOI: 10.1017/s0424820100147491.
- A polypeptide bound by the chaperonin groEL is localized within a central cavity.Braig K, Simon M, Furuya F, Hainfeld J, Horwich A. A polypeptide bound by the chaperonin groEL is localized within a central cavity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1993, 90: 3978-3982. PMID: 8097882, PMCID: PMC46429, DOI: 10.1073/pnas.90.9.3978.
- Protein folding in the cell: functions of two families of molecular chaperone, hsp 60 and TF55-TCP1Horwich A, Willison K. Protein folding in the cell: functions of two families of molecular chaperone, hsp 60 and TF55-TCP1. Philosophical Transactions Of The Royal Society B Biological Sciences 1993, 339: 313-326. PMID: 8098536, DOI: 10.1098/rstb.1993.0030.
- Protein folding in the cell: functions of two families of molecular chaperone, hsp 60 and TF55-TCP1Horwich A, Willison K. Protein folding in the cell: functions of two families of molecular chaperone, hsp 60 and TF55-TCP1. 1993, 57-70. DOI: 10.1007/978-94-011-2108-8_8.
- Two related genes encoding extremely hydrophobic proteins suppress a lethal mutation in the yeast mitochondrial processing enhancing protein.West A, Clark D, Martin J, Neupert W, Hartl F, Horwich A. Two related genes encoding extremely hydrophobic proteins suppress a lethal mutation in the yeast mitochondrial processing enhancing protein. Journal Of Biological Chemistry 1992, 267: 24625-24633. PMID: 1447206, DOI: 10.1016/s0021-9258(18)35810-1.
- Prevention of Protein Denaturation Under Heat Stress by the Chaperonin Hsp60Martin J, Horwich A, Hartl F. Prevention of Protein Denaturation Under Heat Stress by the Chaperonin Hsp60. Science 1992, 258: 995-998. PMID: 1359644, DOI: 10.1126/science.1359644.
- TCP1 complex is a molecular chaperone in tubulin biogenesisYaffe M, Farr G, Miklos D, Horwich A, Sternlicht M, Sternlicht H. TCP1 complex is a molecular chaperone in tubulin biogenesis. Nature 1992, 358: 245-248. PMID: 1630491, DOI: 10.1038/358245a0.
- Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane spaceKoll H, Guiard B, Rassow J, Ostermann J, Horwich A, Neupert W, Hartl F. Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane space. Cell 1992, 68: 1163-1175. PMID: 1347713, DOI: 10.1016/0092-8674(92)90086-r.
- Chapter 26 Chaperonin-mediated protein foldingHorwich A, Caplan S, Wall J, Hartl F. Chapter 26 Chaperonin-mediated protein folding. 1992, 22: 329-337. DOI: 10.1016/s0167-7306(08)60103-9.
- Protein folding causes an arrest of preprotein translocation into mitochondria in vivo.Wienhues U, Becker K, Schleyer M, Guiard B, Tropschug M, Horwich A, Pfanner N, Neupert W. Protein folding causes an arrest of preprotein translocation into mitochondria in vivo. Journal Of Cell Biology 1991, 115: 1601-1609. PMID: 1757464, PMCID: PMC2289212, DOI: 10.1083/jcb.115.6.1601.
- A molecular chaperone from a thermophilic archaebacterium is related to the eukaryotic protein t-complex polypeptide-1Trent J, Nimmesgern E, Wall J, Hartl F, Horwich A. A molecular chaperone from a thermophilic archaebacterium is related to the eukaryotic protein t-complex polypeptide-1. Nature 1991, 354: 490-493. PMID: 1836250, DOI: 10.1038/354490a0.
- Chaperonin-mediated protein folding at the surface of groEL through a 'molten globule'-like intermediateMartin J, Langer T, Boteva R, Schramel A, Horwich A, Hartl F. Chaperonin-mediated protein folding at the surface of groEL through a 'molten globule'-like intermediate. Nature 1991, 352: 36-42. PMID: 1676490, DOI: 10.1038/352036a0.
- Inherited Hepatic Enzyme Defects as Candidates for Liver-Directed Gene TherapyHorwich A. Inherited Hepatic Enzyme Defects as Candidates for Liver-Directed Gene Therapy. 1991, 168: 185-200. PMID: 1893777, DOI: 10.1007/978-3-642-76015-0_9.
- Role of HSP60 in Folding/Assembly of Mitochondrial ProteinsHorwich A, Hartl F, Cheng M. Role of HSP60 in Folding/Assembly of Mitochondrial Proteins. 1991, 165-173. DOI: 10.1007/978-3-642-76679-4_18.
- Mitochondrial protein import.Horwich A, Cheng M, West A, Pollock R. Mitochondrial protein import. 1991, 170: 1-42. PMID: 1760928, DOI: 10.1007/978-3-642-76389-2_1.
- Sorting pathways of mitochondrial inner membrane proteinsMAHLKE K, PFANNER N, MARTIN J, HORWICH A, HARTL F, NEUPERT W. Sorting pathways of mitochondrial inner membrane proteins. The FEBS Journal 1990, 192: 551-555. PMID: 2145157, DOI: 10.1111/j.1432-1033.1990.tb19260.x.
- The mitochondrial stress protein HSP60 as a catalyst of protein foldingHartl F, Martin J, Ostermann J, Horwich A, Neupert W. The mitochondrial stress protein HSP60 as a catalyst of protein folding. Cell Biology International 1990, 14: 8. DOI: 10.1016/0309-1651(90)90140-t.
- Protein import into mitochondria and peroxisomesHorwich A. Protein import into mitochondria and peroxisomes. Current Opinion In Cell Biology 1990, 2: 625-633. PMID: 1979227, DOI: 10.1016/0955-0674(90)90103-l.
- Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification.Summers J, Smith P, Horwich A. Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification. Journal Of Virology 1990, 64: 2819-24. PMID: 2335817, PMCID: PMC249463, DOI: 10.1128/jvi.64.6.2819-2824.1990.
- THE EFFECTS OF EARLY TREATMENT OF HEREDITARY TYROSINEMIA TYPE I IN INFANCY BY ORTHOTOPIC LIVER TRANSPLANTATIONFlye M, RIELY C, HAINLINE B, SASSA S, GUSBERG R, BLAKEMORE K, BARWICK K, HORWICH A. THE EFFECTS OF EARLY TREATMENT OF HEREDITARY TYROSINEMIA TYPE I IN INFANCY BY ORTHOTOPIC LIVER TRANSPLANTATION. Transplantation 1990, 49: 916-921. PMID: 2336709, DOI: 10.1097/00007890-199005000-00017.
- Synthesis of hepadnavirus particles that contain replication-defective duck hepatitis B virus genomes in cultured HuH7 cells.Horwich A, Furtak K, Pugh J, Summers J. Synthesis of hepadnavirus particles that contain replication-defective duck hepatitis B virus genomes in cultured HuH7 cells. Journal Of Virology 1990, 64: 642-50. PMID: 2153230, PMCID: PMC249155, DOI: 10.1128/jvi.64.2.642-650.1990.
- Protein-catalysed protein foldingHorwich A, Neupert W, Hartl F. Protein-catalysed protein folding. Trends In Biotechnology 1990, 8: 126-131. PMID: 1369433, DOI: 10.1016/0167-7799(90)90153-o.
- Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysisOstermann J, Horwich A, Neupert W, Hartl F. Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysis. Nature 1989, 341: 125-130. PMID: 2528694, DOI: 10.1038/341125a0.
- Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondriaCheng M, Hartl F, Martin J, Pollock R, Kalousek F, Neuper W, Hallberg E, Hallberg R, Horwich A. Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 1989, 337: 620-625. PMID: 2645524, DOI: 10.1038/337620a0.
- The processing peptidase of yeast mitochondria: the two co‐operating components MPP and PEP are structurally related.Pollock R, Hartl F, Cheng M, Ostermann J, Horwich A, Neupert W. The processing peptidase of yeast mitochondria: the two co‐operating components MPP and PEP are structurally related. The EMBO Journal 1988, 7: 3493-3500. PMID: 3061797, PMCID: PMC454850, DOI: 10.1002/j.1460-2075.1988.tb03225.x.
- Trisomy 18 associated with ectopia cordis and occipital meningoceleBick D, Markowitz R, Horwich A, Opitz J, Reynolds J. Trisomy 18 associated with ectopia cordis and occipital meningocele. American Journal Of Medical Genetics 1988, 30: 805-810. PMID: 3189399, DOI: 10.1002/ajmg.1320300313.
- Meiotic expression of human ornithine transcarbamylase in the testes of transgenic mice.Kelley K, Chamberlain J, Nolan J, Horwich A, Kalousek F, Eisenstadt J, Herrup K, Rosenberg L. Meiotic expression of human ornithine transcarbamylase in the testes of transgenic mice. Molecular And Cellular Biology 1988, 8: 1821-1825. PMID: 2837657, PMCID: PMC363346, DOI: 10.1128/mcb.8.4.1821.
- Meiotic Expression of Human Ornithine Transcarbamylase in the Testes of Transgenic MiceKelley K, Chamberlain J, Nolan J, Horwich A, Kalousek F, Eisenstadt J, Herrup K, Rosenberg L. Meiotic Expression of Human Ornithine Transcarbamylase in the Testes of Transgenic Mice. Molecular And Cellular Biology 1988, 8: 1821-1825. DOI: 10.1128/mcb.8.4.1821-1825.1988.
- The ornithine transcarbamylase leader peptide directs mitochondrial import through both its midportion structure and net positive charge.Horwich A, Kalousek F, Fenton W, Furtak K, Pollock R, Rosenberg L. The ornithine transcarbamylase leader peptide directs mitochondrial import through both its midportion structure and net positive charge. Journal Of Cell Biology 1987, 105: 669-677. PMID: 3624306, PMCID: PMC2114782, DOI: 10.1083/jcb.105.2.669.
- Import and processing of human ornithine transcarbamoylase precursor by mitochondria from Saccharomyces cerevisiae.Cheng M, Pollock R, Hendrick J, Horwich A. Import and processing of human ornithine transcarbamoylase precursor by mitochondria from Saccharomyces cerevisiae. Proceedings Of The National Academy Of Sciences Of The United States Of America 1987, 84: 4063-4067. PMID: 3295876, PMCID: PMC305022, DOI: 10.1073/pnas.84.12.4063.
- Targeting of Nuclear‐Encoded Proteins to the Mitochondrial Matrix: Implications for Human Genetic DefectsROSENBERG L, FENTON W, HORWICH A, KALOUSEK F, KRAUS J. Targeting of Nuclear‐Encoded Proteins to the Mitochondrial Matrix: Implications for Human Genetic Defects. Annals Of The New York Academy Of Sciences 1986, 488: 99-108. PMID: 3472484, DOI: 10.1111/j.1749-6632.1986.tb54396.x.
- DNA analysis for ornithine transcarbamylase deficiencyRozen R, Fox J, Hack A, Fenton W, Horwich A, Rosenberg L. DNA analysis for ornithine transcarbamylase deficiency. Journal Of Inherited Metabolic Disease 1986, 9: 49-57. PMID: 2878115, DOI: 10.1007/bf01800858.
- Targeting of pre-ornithine transcarbamylase to mitochondria: Definition of critical regions and residues in the leader peptideHorwich A, Kalousek F, Fenton W, Pollock R, Rosenberg L. Targeting of pre-ornithine transcarbamylase to mitochondria: Definition of critical regions and residues in the leader peptide. Cell 1986, 44: 451-459. PMID: 3943133, DOI: 10.1016/0092-8674(86)90466-6.
- DNA Analysis for Ornithine Transcarbamylase DeficiencyRozen R, Fox J, Hack A, Fenton W, Horwich A, Rosenberg L. DNA Analysis for Ornithine Transcarbamylase Deficiency. 1986, 49-57. DOI: 10.1007/978-94-009-4131-1_5.
- Arginine in the leader peptide is required for both import and proteolytic cleavage of a mitochondrial precursor.Horwich A, Kalousek F, Rosenberg L. Arginine in the leader peptide is required for both import and proteolytic cleavage of a mitochondrial precursor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1985, 82: 4930-4933. PMID: 3895227, PMCID: PMC390471, DOI: 10.1073/pnas.82.15.4930.
- Expression of amplified DNA sequences for ornithine transcarbamylase in HeLa cells: arginine residues may be required for mitochondrial import of enzyme precursor.Horwich A, Fenton W, Firgaira F, Fox J, Kolansky D, Mellman I, Rosenberg L. Expression of amplified DNA sequences for ornithine transcarbamylase in HeLa cells: arginine residues may be required for mitochondrial import of enzyme precursor. Journal Of Cell Biology 1985, 100: 1515-1521. PMID: 3988798, PMCID: PMC2113848, DOI: 10.1083/jcb.100.5.1515.
- A leader peptide is sufficient to direct mitochondrial import of a chimeric protein.Horwich A, Kalousek F, Mellman I, Rosenberg L. A leader peptide is sufficient to direct mitochondrial import of a chimeric protein. The EMBO Journal 1985, 4: 1129-35. PMID: 3891325, PMCID: PMC554314, DOI: 10.1002/j.1460-2075.1985.tb03750.x.
- 820 ADDITIONAL RESTRICTION FRAGMENT LENGTH POLYMORPHISMS (RFLS)FOR DETECTION OF ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCYFox J, Rozen R, Fenton W, Horwich A, Rospnherg L. 820 ADDITIONAL RESTRICTION FRAGMENT LENGTH POLYMORPHISMS (RFLS)FOR DETECTION OF ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY. Pediatric Research 1985, 19: 247-247. DOI: 10.1203/00006450-198504000-00850.
- Localization of DNA sequences in region Xp21 of the human X chromosome: search for molecular markers close to the Duchenne muscular dystrophy locus.de Martinville B, Kunkel L, Bruns G, Morlé F, Koenig M, Mandel J, Horwich A, Latt S, Gusella J, Housman D. Localization of DNA sequences in region Xp21 of the human X chromosome: search for molecular markers close to the Duchenne muscular dystrophy locus. American Journal Of Human Genetics 1985, 37: 235-49. PMID: 2984924, PMCID: PMC1684559.
- Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locusRozen R, Fox J, Fenton W, Horwich A, Rosenberg L. Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus. Nature 1985, 313: 815-817. PMID: 2983225, DOI: 10.1038/313815a0.
- A cDNA clone for the precursor of rat mitochondrial ornithine transcarbamylase: comparison of rat and human leader sequences and conservation of catalytic sitesKraus J, Hodges P, Williamson C, Horwich A, Kalousek F, Williams K, Rosenberg L. A cDNA clone for the precursor of rat mitochondrial ornithine transcarbamylase: comparison of rat and human leader sequences and conservation of catalytic sites. Nucleic Acids Research 1985, 13: 943-952. PMID: 3839075, PMCID: PMC341044, DOI: 10.1093/nar/13.3.943.
- Human Ornithine Transcarbamylase Locus Mapped to Band Xp21.1 Near the Duchenne Muscular Dystrophy LocusLindgren V, de Martinville B, Horwich A, Rosenberg L, Francke U. Human Ornithine Transcarbamylase Locus Mapped to Band Xp21.1 Near the Duchenne Muscular Dystrophy Locus. Science 1984, 226: 698-700. PMID: 6494904, DOI: 10.1126/science.6494904.
- Structure and Expression of a Complementary DNA for the Nuclear Coded Precursor of Human Mitochondrial Ornithine TranscarbamylaseHorwich A, Fenton W, Williams K, Kalousek F, Kraus J, Doolittle R, Konigsberg W, Rosenberg L. Structure and Expression of a Complementary DNA for the Nuclear Coded Precursor of Human Mitochondrial Ornithine Transcarbamylase. Science 1984, 224: 1068-1074. PMID: 6372096, DOI: 10.1126/science.6372096.
- GENE DELETION AND RESTRICTION FRAGMENT LENGTH POLYMORPHISM (RFLP) AT THE HUMAN ORNITHINE TRANSCARBAMYLASE (OTC) LOCUSRozen R, Horwich A, Fenton W, Rosenberg L. GENE DELETION AND RESTRICTION FRAGMENT LENGTH POLYMORPHISM (RFLP) AT THE HUMAN ORNITHINE TRANSCARBAMYLASE (OTC) LOCUS. Pediatric Research 1984, 18: 225-225. DOI: 10.1203/00006450-198404001-00791.
- STRATEGIES FOR THE MOLECULAR CLONING OF LOW ABUNDANCE MESSENGER RNAsHorwich A, Kraus J, Rosenberg L. STRATEGIES FOR THE MOLECULAR CLONING OF LOW ABUNDANCE MESSENGER RNAs. 1984, 365-385. DOI: 10.1016/b978-0-12-079280-1.50027-9.
- Molecular cloning of the cDNA coding for rat ornithine transcarbamoylase.Horwich A, Kraus J, Williams K, Kalousek F, Konigsberg W, Rosenberg L. Molecular cloning of the cDNA coding for rat ornithine transcarbamoylase. Proceedings Of The National Academy Of Sciences Of The United States Of America 1983, 80: 4258-4262. PMID: 6576335, PMCID: PMC384016, DOI: 10.1073/pnas.80.14.4258.
- Expression and Stabilization of Microinjected Plasmids Containing the Herpes Simplex Virus Thymidine Kinase Gene and Polyoma Virus DNA in Mouse CellsYamaizumi M, Horwich A, Ruddle F. Expression and Stabilization of Microinjected Plasmids Containing the Herpes Simplex Virus Thymidine Kinase Gene and Polyoma Virus DNA in Mouse Cells. Molecular And Cellular Biology 1983, 3: 511-522. PMID: 6304496, PMCID: PMC368567, DOI: 10.1128/mcb.3.4.511.
- Expression and Stabilization of Microinjected Plasmids Containing the Herpes Simplex Virus Thymidine Kinase Gene and Polyoma Virus DNA in Mouse CellsYamaizumi M, Horwich A, Ruddle F. Expression and Stabilization of Microinjected Plasmids Containing the Herpes Simplex Virus Thymidine Kinase Gene and Polyoma Virus DNA in Mouse Cells. Molecular And Cellular Biology 1983, 3: 511-522. DOI: 10.1128/mcb.3.4.511-522.1983.
- Aqueductal stenosis leading to hydrocephalus—an unusual manifestation of neurofibromatosisHorwich A, Riccardi V, Francke U, Opitz J. Aqueductal stenosis leading to hydrocephalus—an unusual manifestation of neurofibromatosis. American Journal Of Medical Genetics 1983, 14: 577-581. PMID: 6407319, DOI: 10.1002/ajmg.1320140322.
- A father and son with cholestasis and peripheral pulmonic stenosis A distinct form of intrahepatic cholestasisRiely C, LaBrecque D, Ghent C, Horwich A, Klatskin G. A father and son with cholestasis and peripheral pulmonic stenosis A distinct form of intrahepatic cholestasis. The Journal Of Pediatrics 1978, 92: 406-411. PMID: 632979, DOI: 10.1016/s0022-3476(78)80428-4.