A Novel Human Tectonin Protein with Multivalent β-Propeller Folds Interacts with Ficolin and Binds Bacterial LPS 英文参考文献.docVIP

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A Novel Human Tectonin Protein with Multivalent β-Propeller Folds Interacts with Ficolin and Binds Bacterial LPS 英文参考文献.doc

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A Novel Human Tectonin Protein with Multivalent β-Propeller Folds Interacts with Ficolin and Binds Bacterial LPS 英文参考文献

ANovelHumanTectoninProteinwithMultivalentb- PropellerFoldsInteractswithFicolinandBindsBacterial LPS DianaHooiPingLow1,2,ZhiweiAng2,QuanYuan2,VladimirFrecer3,4,BowHo5,JianzhuChen1,6 ,Jeak LingDing1,2 * 1ComputationalandSystemsBiology,Singapore-MITAlliance,Singapore,Singapore,2DepartmentofBiologicalSciences,NationalUniversityofSingapore,Singapore, Singapore,3LaboratoryofMolecularBiostructuralandNanomaterialModeling,AREASciencePark,Trieste,Italy,4CancerResearchInstitute,SlovakAcademyofSciences, Bratislava, Slovakia, 5Department of Microbiology, National University of Singapore, Singapore, Singapore, 6Koch Institute for Integrative Cancer Research and DepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,Massachusetts,UnitedStatesofAmerica Abstract Background:Althoughthehumangenomedatabasehasbeencompletedadecadeago,,50%oftheproteomeremains hypothetical astheirfunctionsareunknown.Theelucidationofthefunctionsofthese hypotheticalproteinscanleadto additionalproteinpathwaysandrevelationofnewcascades.However,manyoftheseinferencesarelimitedtoproteinswith substantialsequencesimilarity.OfparticularinteresthereistheTectonindomain-containingfamilyofproteins. Methodology/PrincipalFindings:WehaveidentifiedhTectonin,ahypotheticalproteininthehumangenomedatabase,as a distant ortholog of the limulus galactose binding protein (GBP). Phylogenetic analysis revealed strong evolutionary conservation of hTectonin homologues from parasite to human. By computational analysis, we showed that both the hTectoninandGBPformb-propellerstructureswithmultipleTectonindomains,eachcontainingb-sheetsof4strandsperb- sheet.hTectoninispresentinthehumanleukocytecDNAlibraryandimmune-relatedcelllines.ItinteractswithM-ficolin,a knownhumancomplementproteinwhoseancienthomolog,carcinolectin(CL5),isthefunctionalproteinpartnerofGBP duringinfection.Yeast2-hybridassayshowedthatonlytheTectonindomainsofhTectoninrecognizethefibrinogen-like domainoftheM-ficolin.Surfaceplasmonresonanceanalysisshowedreal-ti