Simulations of Tubulin Sheet Polymers as Possible Structural Intermediates in Microtubule Assembly 英文参考文献.docVIP

SimulationsofTubulinSheetPolymersasPossible StructuralIntermediatesinMicrotubuleAssembly ZhanghanWu1,2,Hong-WeiWang3,4,WeihuaMu5,6,ZhongcanOuyang5,6,EvaNogales3,7,JianhuaXing2* 1Program in Genetics, Bioinformatics and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America, 2Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America, 3Lawrence Berkeley National Laboratory,Berkeley,California,UnitedStatesofAmerica,4DepartmentofMolecularBiophysicsandBiochemistry,YaleUniversity,NewHaven,Connecticut,UnitedStates ofAmerica,5InstituteofTheoreticalPhysics,TheChineseAcademyofSciences,Beijing,China,6CenterforAdvancedStudy,TsinghuaUniversity,Beijing,China,7Howard HughesMedicalInstitute,DepartmentofMolecularandCellBiology,UniversityofCalifornia,Berkeley,California,UnitedStatesofAmerica Abstract Themicrotubuleassemblyprocesshasbeenextensivelystudied,buttheunderlyingmolecularmechanismremainspoorly understood.Thestructureofanartificiallygeneratedsheetpolymerthatalternatestwotypesoflateralcontactsandthat directlyconvertsintomicrotubules,hasbeenproposedtocorrespondtotheintermediatesheetstructureobservedduring microtubule assembly. We have studied the self-assembly process of GMPCPP tubulins into sheet and microtubule structuresusingthermodynamicanalysisandstochasticsimulations.Withthenovelassumptionsthattubulinscanlaterally interactintwodifferentforms,andallostericallyaffectneighboringlateralinteractions,wecanexplainexistingexperimental observations. At low temperature, the allosteric effect results in the observed sheet structure with alternating lateral interactionsasthethermodynamicallymoststableform.Atnormalmicrotubuleassemblytemperature,ourworkindicates that a class of sheet structures resembling those observed at low temperature is transiently trapped as an intermediate during the assembly process. This work may shed light on the tub