title: Force generation by kinesin and myosin cytoskeletal motor proteins.
abstract: Kinesins and myosins hydrolyze ATP, producing force that drives spindle assembly, vesicle transport and muscle contraction. How do motors do this? Here we discuss mechanisms of motor force transduction, based on their mechanochemical cycles and conformational changes observed in crystal structures. Distortion or twisting of the central β-sheet - proposed to trigger actin-induced Pi and ADP release by myosin, and microtubule-induced ADP release by kinesins - is shown in a movie depicting the transition between myosin ATP-like and nucleotide-free states. Structural changes in the switch I region form a tube that governs ATP hydrolysis and Pi release by the motors, explaining the essential role of switch I in hydrolysis. Comparison of the motor power strokes reveals that each stroke begins with the force-amplifying structure oriented opposite to the direction of rotation or swing. Motors undergo changes in their mechanochemical cycles in response to small-molecule inhibitors, several of which bind to kinesins by induced fit, trapping the motors in a state that resembles a force-producing conformation. An unusual motor activator specifically increases mechanical output by cardiac myosin, potentially providing valuable information about its mechanism of function. Further study is essential to understand motor mechanochemical coupling and energy transduction, and could lead to new therapies to treat human disease.
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: F Jon
authors.initials: FJ
authors.lastname: Kull
authors.forename: Sharyn A
authors.initials: SA
authors.lastname: Endow
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D020409:Molecular Motor Proteins; D000255:Adenosine Triphosphate; D009218:Myosins; D016547:Kinesins