A kinesin motor in a force-producing conformation.
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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.
Amino Acid Sequence
Amino Acid Substitution
Protein Structure, Secondary
Published Version (Please cite this version)10.1186/1472-6807-10-19
Publication InfoHeuston, Elisabeth; Bronner, C Eric; Kull, F Jon; & Endow, Sharyn A (2010). A kinesin motor in a force-producing conformation. BMC Struct Biol, 10. pp. 19. 10.1186/1472-6807-10-19. Retrieved from https://hdl.handle.net/10161/4362.
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Professor of Cell Biology
Research in my laboratory focuses on spindle and chromosome dynamics and the mechanisms that ensure proper chromosome transmission and inheritance in dividing cells. Work in my laboratory and others over the past 5-10 years has identified molecular motor proteins as the force-generating proteins underlying movements of the spindle and chromosomes during cell division. Much of our current effort is directed towards understanding the mechanism of motor function, including the molecular basis