2023
Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention
Krimmer S, Bertoletti N, Suzuki Y, Katic L, Mohanty J, Shu S, Lee S, Lax I, Mi W, Schlessinger J. Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300054120. PMID: 36943885, PMCID: PMC10068818, DOI: 10.1073/pnas.2300054120.Peer-Reviewed Original ResearchMeSH KeywordsCryoelectron MicroscopyHumansLigandsNeoplasmsPhosphorylationProto-Oncogene Proteins c-kitReceptor Protein-Tyrosine KinasesStem Cell FactorConceptsOncogenic KIT mutantsStem cell factorKIT mutantsHomotypic contactsCryo-EM analysisUnexpected structural plasticityLigand stem cell factorElectron microscopy structural analysisReceptor tyrosine kinase KITOncogenic mutantsHematopoietic stem cellsKIT dimerizationTyrosine kinase KITD5 regionPlasma membraneMutational analysisMutantsExtracellular domainGerm cellsHuman cancersSomatic gainCell factorStructural plasticityStem cellsKinase KIT
2020
Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex
Wu X, Siggel M, Ovchinnikov S, Mi W, Svetlov V, Nudler E, Liao M, Hummer G, Rapoport TA. Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex. Science 2020, 368 PMID: 32327568, PMCID: PMC7380553, DOI: 10.1126/science.aaz2449.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCryoelectron MicroscopyEndoplasmic ReticulumEndoplasmic Reticulum-Associated DegradationMembrane GlycoproteinsMembrane ProteinsMolecular Dynamics SimulationMultiprotein ComplexesProtein DomainsProtein FoldingProteolysisSaccharomyces cerevisiae ProteinsUbiquitin-Protein LigasesConceptsHrd1 complexLuminal endoplasmic reticulum proteinsCryo-electron microscopy analysisHrd1 ubiquitin ligaseEndoplasmic reticulum proteinER membraneUbiquitin ligaseProtein degradationStructural basisReticulum proteinsPolypeptide loopMembrane regionsLateral gateLuminal binding sitesBinding sitesLuminal cavityForm twoYos9RetrotranslocationERADMicroscopy analysisSubcomplexLigaseHRD1Proteasome
2017
Structural basis of MsbA-mediated lipopolysaccharide transport
Mi W, Li Y, Yoon SH, Ernst RK, Walz T, Liao M. Structural basis of MsbA-mediated lipopolysaccharide transport. Nature 2017, 549: 233-237. PMID: 28869968, PMCID: PMC5759761, DOI: 10.1038/nature23649.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateATP-Binding Cassette TransportersBacterial ProteinsBiological TransportCell MembraneCryoelectron MicroscopyEscherichia coliHydrophobic and Hydrophilic InteractionsLipid BilayersLipopolysaccharidesModels, MolecularNanostructuresPeriplasmProtein BindingProtein DomainsConceptsPeriplasmic leafletStructural basisSingle-particle cryo-electron microscopyCryo-electron microscopyÅ resolution structureLipid flippasesGram-negative bacteriaLipopolysaccharide transportTransmembrane domainInner membraneCytoplasmic leafletMsbAOuter membraneCell envelopeResolution structureCassette transportersADP-vanadateStructural mechanismsConformational transitionLPS recognitionFunctional stateFlippasesMsbA.Hydrophobic interactionsMembraneCryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3
Schoebel S, Mi W, Stein A, Ovchinnikov S, Pavlovicz R, DiMaio F, Baker D, Chambers MG, Su H, Li D, Rapoport TA, Liao M. Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3. Nature 2017, 548: 352-355. PMID: 28682307, PMCID: PMC5736104, DOI: 10.1038/nature23314.Peer-Reviewed Original Research
2015
Single-particle electron microscopy in the study of membrane protein structure
De Zorzi R, Mi W, Liao M, Walz T. Single-particle electron microscopy in the study of membrane protein structure. Microscopy 2015, 65: 81-96. PMID: 26470917, PMCID: PMC4749050, DOI: 10.1093/jmicro/dfv058.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSingle-particle electron microscopyMembrane protein structuresMembrane proteinsProtein structureAtomic modelElectron microscopyMore membrane proteinsUnprecedented qualityTransient receptor potential (TRP) channel familyDevice cameraChannel familyProteinStructure refinementMicroscopyStructureEnhanced potentialMinor roleCrystalsTechnical advancesTechnical limitationsGreat advantageShort orderFamily
2009
CLIC2-RyR1 Interaction and Structural Characterization by Cryo-electron Microscopy
Meng X, Wang G, Viero C, Wang Q, Mi W, Su XD, Wagenknecht T, Williams AJ, Liu Z, Yin CC. CLIC2-RyR1 Interaction and Structural Characterization by Cryo-electron Microscopy. Journal Of Molecular Biology 2009, 387: 320-334. PMID: 19356589, PMCID: PMC2667806, DOI: 10.1016/j.jmb.2009.01.059.Peer-Reviewed Original ResearchConceptsCryo-electron microscopyChannel activitySkeletal ryanodine receptorsAffinity of ryanodineSkeletal sarcoplasmic reticulum vesiclesSmall proteinsClamp regionConformational changesPhysiological functionsDomain 5Closed stateSingle-channel recordingsStructural familyRyR1 channelsRyanodine receptorSkeletal muscleRyR1VesiclesOpen probabilityRyR channelsChannel 2Channel recordingsEfflux rateSarcoplasmic reticulum vesiclesReticulum vesicles