Ivan Lomakin, PhD
Research Scientist in Dermatology; Affiliated Faculty, Yale Institute for Global Health
Research & Publications
Biography
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Extensive Research Description
The atomic structures of the small 30S ribosomal subunit from the thermophile bacterium Thermus thermophilus (1) and the large 50S ribosomal subunit from the halophile archaebacterium Haloarcula marismortui (2) provided enormous impact on our understanding of the general mechanism of the protein synthesis. This mechanism is most likely the same between prokaryotic and eukaryotic organisms due to the evolutionary conservation of rRNA and ribosomal proteins. However, eukaryotic rRNA is larger and each ribosomal subunit has more proteins then its prokaryotic counterpart. These structural differences reflect more complicated mechanism of ekaryotic translation. They are especially pronounced at the initiation stage. Translation initiation in eukariotes requires more then 12 protein factors (only 3 in prokaryotes) and utilizes the “cap” structure on the 5’-end of mRNA (3). To start protein synthesis small 40S ribosomal subunit scan 5’- untranslated region of mRNA to find initiation AUG codon – process that is unique for eukaryotic organisms (4). We are using X-ray crystallography to find how these functional differences correlate with structural properties of eukaryotic ribosomes.
Coauthors
Research Interests
Acne Vulgaris; Biochemistry; Biophysics; Infections; Molecular Biology; Protein Synthesis Inhibitors; Protein Biosynthesis; Skin and Connective Tissue Diseases
Public Health Interests
Antimicrobial Resistance
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Selected Publications
- Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanismLomakin I, Devarkar S, Patel S, Grada A, Bunick C. Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism. Nucleic Acids Research 2023, 51: 2915-2930. PMID: 36864821, PMCID: PMC10085706, DOI: 10.1093/nar/gkad103.
- Human keratin 1/10‐1B tetramer structures reveal a knob‐pocket mechanism in intermediate filament assemblyEldirany SA, Ho M, Hinbest AJ, Lomakin IB, Bunick CG. Human keratin 1/10‐1B tetramer structures reveal a knob‐pocket mechanism in intermediate filament assembly. The EMBO Journal 2019, 38 PMID: 31036554, PMCID: PMC6545558, DOI: 10.15252/embj.2018100741.
- Antimicrobial peptides targeting bacterial ribosomeLomakin IB, Gagnon MG, Steitz TA. Antimicrobial peptides targeting bacterial ribosome. Oncotarget 2015, 6: 18744-18745. PMID: 26300053, PMCID: PMC4662452, DOI: 10.18632/oncotarget.5114.
- Position of eukaryotic initiation factor eIF5B on the 80S ribosome mapped by directed hydroxyl radical probingUnbehaun A, Marintchev A, Lomakin IB, Didenko T, Wagner G, Hellen C, Pestova TV. Position of eukaryotic initiation factor eIF5B on the 80S ribosome mapped by directed hydroxyl radical probing. The EMBO Journal 2007, 26: 3109-3123. PMID: 17568775, PMCID: PMC1914099, DOI: 10.1038/sj.emboj.7601751.
- The Crystal Structure of Yeast Fatty Acid Synthase, a Cellular Machine with Eight Active Sites Working TogetherLomakin IB, Xiong Y, Steitz TA. The Crystal Structure of Yeast Fatty Acid Synthase, a Cellular Machine with Eight Active Sites Working Together. Cell 2007, 129: 319-332. PMID: 17448991, DOI: 10.1016/j.cell.2007.03.013.
- Insight into the Tumor Suppression Mechanism from the Structure of Human Polypyrimidine Splicing Factor (PSF/SFPQ) Complexed with a 30mer RNA from Murine Virus-like 30S Transcript‑1Wang J, Sachpatzidis A, Christian TD, Lomakin IB, Garen A, Konigsberg WH. Insight into the Tumor Suppression Mechanism from the Structure of Human Polypyrimidine Splicing Factor (PSF/SFPQ) Complexed with a 30mer RNA from Murine Virus-like 30S Transcript‑1. Biochemistry 2022, 61: 1723-1734. PMID: 35998361, DOI: 10.1021/acs.biochem.2c00192.
- Recent insight into intermediate filament structureEldirany SA, Lomakin IB, Ho M, Bunick CG. Recent insight into intermediate filament structure. Current Opinion In Cell Biology 2020, 68: 132-143. PMID: 33190098, PMCID: PMC7925366, DOI: 10.1016/j.ceb.2020.10.001.
- Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNAYuan S, Peng L, Park JJ, Hu Y, Devarkar SC, Dong MB, Shen Q, Wu S, Chen S, Lomakin IB, Xiong Y. Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA. Molecular Cell 2020, 80: 1055-1066.e6. PMID: 33188728, PMCID: PMC7833686, DOI: 10.1016/j.molcel.2020.10.034.
- Coronavirus Nsp1: Immune Response Suppression and Protein Expression InhibitionYuan S, Balaji S, Lomakin IB, Xiong Y. Coronavirus Nsp1: Immune Response Suppression and Protein Expression Inhibition. Frontiers In Microbiology 2021, 12: 752214. PMID: 34659188, PMCID: PMC8512706, DOI: 10.3389/fmicb.2021.752214.
- Physical Association of Eukaryotic Initiation Factor 4G (eIF4G) with eIF4A Strongly Enhances Binding of eIF4G to the Internal Ribosomal Entry Site of Encephalomyocarditis Virus and Is Required for Internal Initiation of TranslationLomakin I, Hellen C, Pestova T. Physical Association of Eukaryotic Initiation Factor 4G (eIF4G) with eIF4A Strongly Enhances Binding of eIF4G to the Internal Ribosomal Entry Site of Encephalomyocarditis Virus and Is Required for Internal Initiation of Translation. Molecular And Cellular Biology 2000, 20: 6019-6029. PMID: 10913184, PMCID: PMC86078, DOI: 10.1128/mcb.20.16.6019-6029.2000.
- A Conserved HEAT Domain within eIF4G Directs Assembly of the Translation Initiation MachineryMarcotrigiano J, Lomakin I, Sonenberg N, Pestova T, Hellen C, Burley S. A Conserved HEAT Domain within eIF4G Directs Assembly of the Translation Initiation Machinery. Molecular Cell 2001, 7: 193-203. PMID: 11172724, DOI: 10.1016/s1097-2765(01)00167-8.
- Molecular mechanisms of translation initiation in eukaryotesPestova T, Kolupaeva V, Lomakin I, Pilipenko E, Shatsky I, Agol V, Hellen C. Molecular mechanisms of translation initiation in eukaryotes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 7029-7036. PMID: 11416183, PMCID: PMC34618, DOI: 10.1073/pnas.111145798.
- Dendritic BC1 RNA: Functional Role in Regulation of Translation InitiationWang H, Iacoangeli A, Popp S, Muslimov IA, Imataka H, Sonenberg N, Lomakin IB, Tiedge H. Dendritic BC1 RNA: Functional Role in Regulation of Translation Initiation. Journal Of Neuroscience 2002, 22: 10232-10241. PMID: 12451124, PMCID: PMC1828542, DOI: 10.1523/jneurosci.22-23-10232.2002.
- Position of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit determined by directed hydroxyl radical probingLomakin IB, Kolupaeva VG, Marintchev A, Wagner G, Pestova TV. Position of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit determined by directed hydroxyl radical probing. Genes & Development 2003, 17: 2786-2797. PMID: 14600024, PMCID: PMC280627, DOI: 10.1101/gad.1141803.
- The fidelity of translation initiation: reciprocal activities of eIF1, IF3 and YciHLomakin IB, Shirokikh NE, Yusupov MM, Hellen C, Pestova TV. The fidelity of translation initiation: reciprocal activities of eIF1, IF3 and YciH. The EMBO Journal 2005, 25: 196-210. PMID: 16362046, PMCID: PMC1356347, DOI: 10.1038/sj.emboj.7600904.
- The joining of ribosomal subunits in eukaryotes requires eIF5BPestova T, Lomakin I, Lee J, Choi S, Dever T, Hellen C. The joining of ribosomal subunits in eukaryotes requires eIF5B. Nature 2000, 403: 332-335. PMID: 10659855, DOI: 10.1038/35002118.
- The initiation of mammalian protein synthesis and mRNA scanning mechanismLomakin IB, Steitz TA. The initiation of mammalian protein synthesis and mRNA scanning mechanism. Nature 2013, 500: 307-311. PMID: 23873042, PMCID: PMC3748252, DOI: 10.1038/nature12355.
- Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formationLomakin IB, Dmitriev SE, Steitz TA. Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 528-533. PMID: 30584092, PMCID: PMC6329987, DOI: 10.1073/pnas.1809688116.
- Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosomeBatool Z, Lomakin IB, Polikanov YS, Bunick CG. Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 20530-20537. PMID: 32817463, PMCID: PMC7456112, DOI: 10.1073/pnas.2008671117.
- The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocinRoy RN, Lomakin IB, Gagnon MG, Steitz TA. The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nature Structural & Molecular Biology 2015, 22: 466-469. PMID: 25984972, PMCID: PMC4456192, DOI: 10.1038/nsmb.3031.
- Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronavirusesDevarkar S, Vetick M, Balaji S, Lomakin I, Yang L, Jin D, Gilbert W, Chen S, Xiong Y. Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses. Cell Reports 2023, 42: 113156. PMID: 37733586, DOI: 10.1016/j.celrep.2023.113156.
- 1041 Atomic resolution structure of the cutibacterium acnes ribosome reveals the mechanism of protein synthesis inhibition by the antibiotic sarecyclineLomakin I, Devarkar S, Patel S, Grada A, Bunick C. 1041 Atomic resolution structure of the cutibacterium acnes ribosome reveals the mechanism of protein synthesis inhibition by the antibiotic sarecycline. Journal Of Investigative Dermatology 2023, 143: s178. DOI: 10.1016/j.jid.2023.03.1052.
- Structural properties of target binding by profilaggrin A and B domains and other S100 fused-type calcium-binding proteinsHinbest AJ, Kim SR, Eldirany SA, Lomakin IB, Watson J, Ho M, Bunick CG. Structural properties of target binding by profilaggrin A and B domains and other S100 fused-type calcium-binding proteins. Journal Of Dermatological Science 2020, 100: 39-49. PMID: 32893105, PMCID: PMC7752840, DOI: 10.1016/j.jdermsci.2020.08.009.
- 576 Crystal structure of sarecycline bound to the 70S bacterial ribosome reveals structural differences from other tetracyclines at atomic resolutionBatool Z, Lomakin I, Polikanov Y, Bunick C. 576 Crystal structure of sarecycline bound to the 70S bacterial ribosome reveals structural differences from other tetracyclines at atomic resolution. Journal Of Investigative Dermatology 2020, 140: s79. DOI: 10.1016/j.jid.2020.03.586.
- Crystal Structure of Keratin 1/10(C401A) 2B Heterodimer Demonstrates a Proclivity for the C-Terminus of Helix 2B to Form Higher Order Molecular Contacts.Lomakin IB, Hinbest AJ, Ho M, Eldirany SA, Bunick CG. Crystal Structure of Keratin 1/10(C401A) 2B Heterodimer Demonstrates a Proclivity for the C-Terminus of Helix 2B to Form Higher Order Molecular Contacts. The Yale Journal Of Biology And Medicine 2020, 93: 3-17. PMID: 32226330, PMCID: PMC7087056.
- Crystal structure of the C-terminal domain of DENRLomakin IB, De S, Wang J, Borkar AN, Steitz TA. Crystal structure of the C-terminal domain of DENR. Computational And Structural Biotechnology Journal 2020, 18: 696-704. PMID: 32257053, PMCID: PMC7114459, DOI: 10.1016/j.csbj.2020.03.009.
- Abstract P-17: Structural and Functional Insights into Eukaryotic Translation Reinitiation and Ribosome Recycling Orchestrated by eIF2D and MCT-1/DENRMakeeva D, Stolboushkina E, Lomakin I, Dmitriev S. Abstract P-17: Structural and Functional Insights into Eukaryotic Translation Reinitiation and Ribosome Recycling Orchestrated by eIF2D and MCT-1/DENR. International Journal Of Biomedicine 2019, 9: s24-s24. DOI: 10.21103/ijbm.9.suppl_1.p17.
- 339 Keratin 1–keratin 10 helix 1B tetramer crystal structures reveal a knob-pocket mechanism important for proper assembly of intermediate filamentsHinbest A, Ho M, Eldirany S, Lomakin I, Bunick C. 339 Keratin 1–keratin 10 helix 1B tetramer crystal structures reveal a knob-pocket mechanism important for proper assembly of intermediate filaments. Journal Of Investigative Dermatology 2019, 139: s58. DOI: 10.1016/j.jid.2019.03.415.
- 689 The x-ray crystal structure of human keratin 1 with S233L mutation demonstrates mechanism of pathogenic tonotubular keratin formation leading to epidermolytic palmoplantar keratodermaEldirany S, Hinbest A, Lomakin I, Bunick C. 689 The x-ray crystal structure of human keratin 1 with S233L mutation demonstrates mechanism of pathogenic tonotubular keratin formation leading to epidermolytic palmoplantar keratoderma. Journal Of Investigative Dermatology 2018, 138: s117. DOI: 10.1016/j.jid.2018.03.698.
- 713 The crystal structure of keratin 1/10(Cys401Ala) helix 2B heterodimer determined at 2.0 Å resolutionLomakin I, Hinbest A, Bunick C. 713 The crystal structure of keratin 1/10(Cys401Ala) helix 2B heterodimer determined at 2.0 Å resolution. Journal Of Investigative Dermatology 2018, 138: s121. DOI: 10.1016/j.jid.2018.03.722.
- EIF1AX and NRAS Mutations Co-occur and Cooperate in Low-Grade Serous Ovarian CarcinomasEtemadmoghadam D, Azar WJ, Lei Y, Moujaber T, Garsed DW, Kennedy CJ, Fereday S, Mitchell C, Chiew YE, Hendley J, Sharma R, Harnett PR, Li J, Christie EL, Patch AM, George J, Au-Yeung G, Mir Arnau G, Holloway TP, Semple T, Pearson JV, Waddell N, Grimmond SM, Köbel M, Rizos H, Lomakin IB, Bowtell DDL, deFazio A. EIF1AX and NRAS Mutations Co-occur and Cooperate in Low-Grade Serous Ovarian Carcinomas. Cancer Research 2017, 77: 4268-4278. PMID: 28646021, DOI: 10.1158/0008-5472.can-16-2224.
- Crystal Structure of the C-terminal Domain of Human eIF2D and Its Implications on Eukaryotic Translation InitiationVaidya AT, Lomakin IB, Joseph NN, Dmitriev SE, Steitz TA. Crystal Structure of the C-terminal Domain of Human eIF2D and Its Implications on Eukaryotic Translation Initiation. Journal Of Molecular Biology 2017, 429: 2765-2771. PMID: 28736176, PMCID: PMC5572308, DOI: 10.1016/j.jmb.2017.07.015.
- Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1Lomakin IB, Stolboushkina EA, Vaidya AT, Zhao C, Garber MB, Dmitriev SE, Steitz TA. Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. Cell Reports 2017, 20: 521-528. PMID: 28723557, PMCID: PMC5551485, DOI: 10.1016/j.celrep.2017.06.025.
- Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibitionGagnon MG, Roy RN, Lomakin IB, Florin T, Mankin AS, Steitz TA. Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. Nucleic Acids Research 2016, 44: 2439-2450. PMID: 26809677, PMCID: PMC4797290, DOI: 10.1093/nar/gkw018.
- Binding of eukaryotic initiation factor 3 to ribosomal 40S subunits and its role in ribosomal dissociation and anti-associationKolupaeva VG, Unbehaun A, Lomakin IB, Hellen CU, Pestova TV. Binding of eukaryotic initiation factor 3 to ribosomal 40S subunits and its role in ribosomal dissociation and anti-association. RNA 2005, 11: 470-486. PMID: 15703437, PMCID: PMC1370736, DOI: 10.1261/rna.7215305.
- Position of the CrPV IRES on the 40S subunit and factor dependence of IRES/80S ribosome assemblyPestova TV, Lomakin IB, Hellen CU. Position of the CrPV IRES on the 40S subunit and factor dependence of IRES/80S ribosome assembly. EMBO Reports 2004, 5: 906-913. PMID: 15332113, PMCID: PMC1299141, DOI: 10.1038/sj.embor.7400240.
- Transcript cleavage factors GreA and GreB act as transient catalytic components of RNA polymeraseLaptenko O, Lee J, Lomakin I, Borukhov S. Transcript cleavage factors GreA and GreB act as transient catalytic components of RNA polymerase. The EMBO Journal 2003, 22: 6322-6334. PMID: 14633991, PMCID: PMC291851, DOI: 10.1093/emboj/cdg610.
- Eukaryotic Initiation Factors 4G and 4A Mediate Conformational Changes Downstream of the Initiation Codon of the Encephalomyocarditis Virus Internal Ribosomal Entry SiteKolupaeva VG, Lomakin IB, Pestova TV, Hellen CU. Eukaryotic Initiation Factors 4G and 4A Mediate Conformational Changes Downstream of the Initiation Codon of the Encephalomyocarditis Virus Internal Ribosomal Entry Site. Molecular And Cellular Biology 2003, 23: 687-698. PMID: 12509466, PMCID: PMC151537, DOI: 10.1128/mcb.23.2.687-698.2003.
- The Functional Role of Basic Patch, a Structural Element ofEscherichia coli Transcript Cleavage Factors GreA and GreB*Kulish D, Lee J, Lomakin I, Nowicka B, Das A, Darst S, Normet K, Borukhov S. The Functional Role of Basic Patch, a Structural Element ofEscherichia coli Transcript Cleavage Factors GreA and GreB*. Journal Of Biological Chemistry 2000, 275: 12789-12798. PMID: 10777576, DOI: 10.1074/jbc.275.17.12789.