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dc.contributor.authorHeuston, E
dc.contributor.authorBronner, CE
dc.contributor.authorKull, FJ
dc.contributor.authorEndow, SA
dc.coverage.spatialEngland
dc.date.accessioned2011-06-21T17:29:38Z
dc.date.issued2010-07-05
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/20602775
dc.identifier1472-6807-10-19
dc.identifier.citationBMC Struct Biol, 2010, 10 pp. 19 - ?
dc.identifier.urihttp://hdl.handle.net/10161/4362
dc.description.abstractBACKGROUND: Kinesin motors hydrolyze ATP to produce force and move along microtubules, converting chemical energy into work by a mechanism that is only poorly understood. Key transitions and intermediate states in the process are still structurally uncharacterized, and remain outstanding questions in the field. Perturbing the motor by introducing point mutations could stabilize transitional or unstable states, providing critical information about these rarer states. RESULTS: Here we show that mutation of a single residue in the kinesin-14 Ncd causes the motor to release ADP and hydrolyze ATP faster than wild type, but move more slowly along microtubules in gliding assays, uncoupling nucleotide hydrolysis from force generation. A crystal structure of the motor shows a large rotation of the stalk, a conformation representing a force-producing stroke of Ncd. Three C-terminal residues of Ncd, visible for the first time, interact with the central beta-sheet and dock onto the motor core, forming a structure resembling the kinesin-1 neck linker, which has been proposed to be the primary force-generating mechanical element of kinesin-1. CONCLUSIONS: Force generation by minus-end Ncd involves docking of the C-terminus, which forms a structure resembling the kinesin-1 neck linker. The mechanism by which the plus- and minus-end motors produce force to move to opposite ends of the microtubule appears to involve the same conformational changes, but distinct structural linkers. Unstable ADP binding may destabilize the motor-ADP state, triggering Ncd stalk rotation and C-terminus docking, producing a working stroke of the motor.
dc.format.extent19 - ?
dc.languageeng
dc.language.isoen_US
dc.relation.ispartofBMC Struct Biol
dc.relation.isversionof10.1186/1472-6807-10-19
dc.subjectAdenosine Diphosphate
dc.subjectAdenosine Triphosphate
dc.subjectAmino Acid Sequence
dc.subjectAmino Acid Substitution
dc.subjectAnimals
dc.subjectBinding Sites
dc.subjectCrystallography, X-Ray
dc.subjectDrosophila Proteins
dc.subjectDrosophila melanogaster
dc.subjectHydrolysis
dc.subjectKinesin
dc.subjectKinetics
dc.subjectMicrotubules
dc.subjectModels, Molecular
dc.subjectMutation
dc.subjectProtein Structure, Secondary
dc.subjectRotation
dc.titleA kinesin motor in a force-producing conformation.
dc.title.alternative
dc.typeJournal article
dc.description.versionVersion of Record
duke.date.pubdate2010-7-5
duke.description.endpage19
duke.description.issue
duke.description.startpage19
duke.description.volume10
dc.relation.journalBmc Structural Biology
pubs.author-urlhttp://www.ncbi.nlm.nih.gov/pubmed/20602775
pubs.organisational-groupBasic Science Departments
pubs.organisational-groupCell Biology
pubs.organisational-groupDuke
pubs.organisational-groupSchool of Medicine
pubs.publication-statusPublished online
pubs.volume10
dc.identifier.eissn1472-6807


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