Role of Hsp70 ATPase Domain Intrinsic Dynamics and Sequence Evolution in Enabling its Functional Interactions with NEFs 英文参考文献.docVIP
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Role of Hsp70 ATPase Domain Intrinsic Dynamics and Sequence Evolution in Enabling its Functional Interactions with NEFs 英文参考文献
RoleofHsp70ATPaseDomainIntrinsicDynamicsand
SequenceEvolutioninEnablingitsFunctional
InteractionswithNEFs
YingLiu1,LilaM.Gierasch2,IvetBahar1*
1DepartmentofComputationalandSystemsBiology,SchoolofMedicine,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2Departmentof
BiochemistryandMolecularBiology,andDepartmentofChemistry,UniversityofMassachusettsAmherst,Amherst,Massachusetts,UnitedStatesofAmerica
Abstract
Catalysis of ADP-ATP exchange by nucleotide exchange factors (NEFs) is central to the activity of Hsp70 molecular
chaperones.Yet,themechanismofinteractionofthisfamilyofchaperoneswithNEFsisnotwellunderstoodinthecontext
ofthesequenceevolutionandstructuraldynamicsofHsp70ATPasedomains.WestudiedtheinteractionsofHsp70ATPase
domainswithfourdifferentNEFsonthebasisoftheevolutionarytraceandco-evolutionoftheATPasedomainsequence,
combinedwithelasticnetworkmodelingofthecollectivedynamicsofthecomplexes.Ourstudyrevealsasubtlebalance
between the intrinsic (to the ATPase domain) and specific (to interactions with NEFs) mechanisms shared by the four
complexes. Two classes of key residues are distinguished in the Hsp70 ATPase domain: (i) highly conserved residues,
involvedinnucleotidebinding,whichmediate,viaaglobalhinge-bending,theATPasedomainopeningirrespectiveofNEF
binding,and(ii)not-conservedbutco-evolvedandhighlymobileresidues,engagedinspecificinteractionswithNEFs(e.g.,
N57,R258,R262,E283,D285).Theobservedinterplaybetweentheserespectiveintrinsic(pre-existing,structure-encoded)
and specific (co-evolved, sequence-dependent) interactions provides us with insights into the allosteric dynamics and
functionalevolutionofthemodularHsp70ATPasedomain.
Citation:LiuY,GieraschLM,BaharI(2010)RoleofHsp70ATPaseDomainIntrinsicDynamicsandSequenceEvolutioninEnablingitsFunctionalInteractionswith
NEFs.PLoSComputBiol6(9):e1000931.doi:10.1371/journal.pcbi.1000931
Editor:BurkhardRost,ColumbiaUniversity,UnitedStatesofAmerica
ReceivedMarch23,2010;AcceptedAugust16,2010;PublishedSepte
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