2010
Two Independent Histidines, One in Human Prolactin and One in Its Receptor, Are Critical for pH-dependent Receptor Recognition and Activation*
Kulkarni MV, Tettamanzi MC, Murphy JW, Keeler C, Myszka DG, Chayen NE, Lolis EJ, Hodsdon ME. Two Independent Histidines, One in Human Prolactin and One in Its Receptor, Are Critical for pH-dependent Receptor Recognition and Activation*. Journal Of Biological Chemistry 2010, 285: 38524-38533. PMID: 20889499, PMCID: PMC2992285, DOI: 10.1074/jbc.m110.172072.Peer-Reviewed Original ResearchStructure of the EF-hand domain of polycystin-2 suggests a mechanism for Ca2+-dependent regulation of polycystin-2 channel activity
Petri ET, Ćelić A, Kennedy SD, Ehrlich BE, Boggon TJ, Hodsdon ME. Structure of the EF-hand domain of polycystin-2 suggests a mechanism for Ca2+-dependent regulation of polycystin-2 channel activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 9176-9181. PMID: 20439752, PMCID: PMC2889120, DOI: 10.1073/pnas.0912295107.Peer-Reviewed Original ResearchConceptsEF-hand domainPolycystin-2Dependent protein interactionsTerminal cytoplasmic tailSequence conservation analysisPC2 channel activityChannel activityDependent conformational changesMechanism of regulationEF-hand motifsHLH motifHelix motifCytoplasmic tailCoil domainProtein interactionsConservation analysisDependent regulationNMR structureSensitive regulationConformational changesSensitive regulatorFunctional regionsFlexible linkerPermeable channelsPC2 activity
2009
A PH domain within OCRL bridges clathrin‐mediated membrane trafficking to phosphoinositide metabolism
Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P. A PH domain within OCRL bridges clathrin‐mediated membrane trafficking to phosphoinositide metabolism. The EMBO Journal 2009, 28: 1831-1842. PMID: 19536138, PMCID: PMC2711190, DOI: 10.1038/emboj.2009.155.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesClathrinCoated VesiclesEndocytosisHeLa CellsHumansModels, MolecularMolecular Sequence DataMutationNuclear Magnetic Resonance, BiomolecularPhosphatidylinositolsPhospholipidsPhosphoric Monoester HydrolasesProtein ConformationProtein Structure, TertiaryRatsSequence AlignmentConceptsPH domainNH2-terminal portionEndocytic clathrin-coated pitsClathrin-binding siteClathrin-coated pitsNMR structure determinationNH2-terminal regionCOOH-terminal regionClathrin-box motifsMembrane traffickingEvolutionary pressureSimilar proteinsINPP5BOCRLSpecialized functionsSequence dissimilarityLowe syndromePhosphoinositide metabolismDent's diseaseHeavy chainMutationsRecruitment efficiencyStructure determinationMetabolismDomainContribution of individual histidines to the global stability of human prolactin
Keeler C, Tettamanzi MC, Meshack S, Hodsdon ME. Contribution of individual histidines to the global stability of human prolactin. Protein Science 2009, 18: 909-920. PMID: 19384991, PMCID: PMC2771294, DOI: 10.1002/pro.100.Peer-Reviewed Original ResearchConceptsIndividual histidineClosest evolutionary cousinsEvolutionary roleDouble mutant cyclesHomologous residuesEvolutionary cousinsNearby histidineExtracellular domainNative proteinTertiary structureStability of hGHNative stateMutant cyclesHuman growth hormoneHistidineStructural interactionsHuman prolactinResiduesPolypeptide hormonesPhysiologic pH rangeFunctional propertiesStructural locationAffinityProteinMutations
2008
Analysis of Site-Specific Histidine Protonation in Human Prolactin ,
Tettamanzi MC, Keeler C, Meshack S, Hodsdon ME. Analysis of Site-Specific Histidine Protonation in Human Prolactin ,. Biochemistry 2008, 47: 8638-8647. PMID: 18652486, PMCID: PMC2766358, DOI: 10.1021/bi800444t.Peer-Reviewed Original ResearchConceptsPH-dependent regulationSite-directed mutagenesisExtracellular domainHistidine residuesHistidine protonationStatistical supportHPRL receptorFunctional propertiesHuman prolactinProtein surfaceBiophysical mechanismsBiophysical originApparent midpointEquilibrium dissociation constantsHistidineResiduesProtein hormonesDetailed understandingCooperativity constantsSurprising numberDissociation rateMutagenesisDissociation constantsProteinNMR spectroscopy
2007
The Kinetics of Binding Human Prolactin, but Not Growth Hormone, to the Prolactin Receptor Vary over a Physiologic pH Range †
Keeler C, Jablonski EM, Albert YB, Taylor BD, Myszka DG, Clevenger CV, Hodsdon ME. The Kinetics of Binding Human Prolactin, but Not Growth Hormone, to the Prolactin Receptor Vary over a Physiologic pH Range †. Biochemistry 2007, 46: 2398-2410. PMID: 17279774, DOI: 10.1021/bi061958v.Peer-Reviewed Original Research
2006
Solution structure and backbone dynamics of an N‐terminal ubiquitin‐like domain in the GLUT4‐regulating protein, TUG
Tettamanzi MC, Yu C, Bogan JS, Hodsdon ME. Solution structure and backbone dynamics of an N‐terminal ubiquitin‐like domain in the GLUT4‐regulating protein, TUG. Protein Science 2006, 15: 498-508. PMID: 16501224, PMCID: PMC2249771, DOI: 10.1110/ps.051901806.Peer-Reviewed Original ResearchConceptsN-terminal ubiquitin-like domainUbiquitin-like domainC-terminal diglycine motifPotential protein-protein interaction sitesN-terminal UBL domainAcceptor lysine residuesBackbone dynamicsProtein-protein interactionsProtein-protein interaction sitesSpecific cellular processesUbiquitin-proteasome pathwayLack of conservationProtein modification reactionUBL domainCellular processesDiglycine motifExocytic machineryUbiquitin recognitionAcceptor lysinePlasma membraneMolecular basisInsulin stimulationLysine residuesMembrane vesiclesTertiary structure
2004
Consequences of Binding an S-Adenosylmethionine Analogue on the Structure and Dynamics of the Thiopurine Methyltransferase Protein Backbone †
Scheuermann TH, Keeler C, Hodsdon ME. Consequences of Binding an S-Adenosylmethionine Analogue on the Structure and Dynamics of the Thiopurine Methyltransferase Protein Backbone †. Biochemistry 2004, 43: 12198-12209. PMID: 15379558, DOI: 10.1021/bi0492556.Peer-Reviewed Original ResearchConceptsNMR chemical shift mapping experimentsChemical shift mapping experimentsNative structureS-adenosylmethionineProteasomal-dependent pathwayCatalytic mechanismProtein backboneIntracellular degradationIndirect conformational changesS-adenosylmethionine analogPresence of sinefunginBacterial orthologuesChemical shift changesProtein backbone dynamicsPseudomonas syringaeSubstrate recognitionProtein sequencesSAM analoguesConformational changesNMR spectroscopyBackbone dynamicsMapping experimentsBackbone mobilitySinefunginNMR relaxation
2003
Tertiary Structure of Thiopurine Methyltransferase from Pseudomonas syringae, a Bacterial Orthologue of a Polymorphic, Drug-metabolizing Enzyme
Scheuermann TH, Lolis E, Hodsdon ME. Tertiary Structure of Thiopurine Methyltransferase from Pseudomonas syringae, a Bacterial Orthologue of a Polymorphic, Drug-metabolizing Enzyme. Journal Of Molecular Biology 2003, 333: 573-585. PMID: 14556746, DOI: 10.1016/j.jmb.2003.08.039.Peer-Reviewed Original ResearchConceptsTertiary structureBacterial orthologuesPseudomonas syringaeConsensus topologyProteasomal-dependent pathwayEnzymatic activitySAM-dependent methyltransferasesUnstructured N-terminusSequence similarityThree-dimensional structureShares 45Dependent transmethylationProtein sequencesN-terminusHuman enzymePolymorphic proteinsBiochemical studiesS-adenosylmethionineOrthologuesSyringaeMethyltransferaseTissue enzymatic activityThiopurine methyltransferaseIntracellular conversionMultiple insertions