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dc.contributor.author Heuston, E
dc.contributor.author Bronner, CE
dc.contributor.author Kull, FJ
dc.contributor.author Endow, SA
dc.coverage.spatial England
dc.date.accessioned 2011-06-21T17:29:38Z
dc.date.issued 2010-07-05
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20602775
dc.identifier 1472-6807-10-19
dc.identifier.citation BMC Struct Biol, 2010, 10 pp. 19 - ?
dc.identifier.uri http://hdl.handle.net/10161/4362
dc.description.abstract BACKGROUND: 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.extent 19 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof BMC Struct Biol
dc.relation.isversionof 10.1186/1472-6807-10-19
dc.subject Adenosine Diphosphate
dc.subject Adenosine Triphosphate
dc.subject Amino Acid Sequence
dc.subject Amino Acid Substitution
dc.subject Animals
dc.subject Binding Sites
dc.subject Crystallography, X-Ray
dc.subject Drosophila Proteins
dc.subject Drosophila melanogaster
dc.subject Hydrolysis
dc.subject Kinesin
dc.subject Kinetics
dc.subject Microtubules
dc.subject Models, Molecular
dc.subject Mutation
dc.subject Protein Structure, Secondary
dc.subject Rotation
dc.title A kinesin motor in a force-producing conformation.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-7-5 en_US
duke.description.endpage 19 en_US
duke.description.issue en_US
duke.description.startpage 19 en_US
duke.description.volume 10 en_US
dc.relation.journal Bmc Structural Biology en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20602775
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Cell Biology
pubs.publication-status Published online
pubs.volume 10
dc.identifier.eissn 1472-6807

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