Kinesin Moves by an Asymmetric Hand-over-hand Mechanism

Overview

Journal Science

Specialty Science

Date 2003 Dec 6

PMID 14657506

Citations 178

Authors

Charles L Asbury

Adrian N Fehr

Steven M Block

Affiliations

Soon will be listed here.

Abstract

Kinesin is a double-headed motor protein that moves along microtubules in 8-nanometer steps. Two broad classes of model have been invoked to explain kinesin movement: hand-over-hand and inchworm. In hand-over-hand models, the heads exchange leading and trailing roles with every step, whereas no such exchange is postulated for inchworm models, where one head always leads. By measuring the stepwise motion of individual enzymes, we find that some kinesin molecules exhibit a marked alternation in the dwell times between sequential steps, causing these motors to "limp" along the microtubule. Limping implies that kinesin molecules strictly alternate between two different conformations as they step, indicative of an asymmetric, hand-over-hand mechanism.

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References

Schnitzer M, Block S . Kinesin hydrolyses one ATP per 8-nm step. Nature. 1997; 388(6640):386-90. DOI: 10.1038/41111. View

Bryant Z, Stone M, Gore J, Smith S, Cozzarelli N, Bustamante C . Structural transitions and elasticity from torque measurements on DNA. Nature. 2003; 424(6946):338-41. DOI: 10.1038/nature01810. View

Yildiz A, Forkey J, McKinney S, Ha T, Goldman Y, Selvin P . Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization. Science. 2003; 300(5628):2061-5. DOI: 10.1126/science.1084398. View

Rosenfeld S, Fordyce P, Jefferson G, King P, Block S . Stepping and stretching. How kinesin uses internal strain to walk processively. J Biol Chem. 2003; 278(20):18550-6. PMC: 1533991. DOI: 10.1074/jbc.M300849200. View

Block S, Asbury C, Shaevitz J, Lang M . Probing the kinesin reaction cycle with a 2D optical force clamp. Proc Natl Acad Sci U S A. 2003; 100(5):2351-6. PMC: 151344. DOI: 10.1073/pnas.0436709100. View

Lang M, Asbury C, Shaevitz J, Block S . An automated two-dimensional optical force clamp for single molecule studies. Biophys J. 2002; 83(1):491-501. PMC: 1302163. DOI: 10.1016/S0006-3495(02)75185-0. View

Hua W, Chung J, Gelles J . Distinguishing inchworm and hand-over-hand processive kinesin movement by neck rotation measurements. Science. 2002; 295(5556):844-8. DOI: 10.1126/science.1063089. View

Gelles J, Schnapp B, Sheetz M . Tracking kinesin-driven movements with nanometre-scale precision. Nature. 1988; 331(6155):450-3. DOI: 10.1038/331450a0. View

Rice S, Lin A, Safer D, Hart C, Naber N, Carragher B . A structural change in the kinesin motor protein that drives motility. Nature. 2000; 402(6763):778-84. DOI: 10.1038/45483. View

10.

Hoenger A, Thormahlen M, Doerhoefer M, Goldie K, Muller J, Mandelkow E . A new look at the microtubule binding patterns of dimeric kinesins. J Mol Biol. 2000; 297(5):1087-103. DOI: 10.1006/jmbi.2000.3627. View

11.

Visscher K, Schnitzer M, Block S . Single kinesin molecules studied with a molecular force clamp. Nature. 1999; 400(6740):184-9. DOI: 10.1038/22146. View

12.

Coy D, Wagenbach M, Howard J . Kinesin takes one 8-nm step for each ATP that it hydrolyzes. J Biol Chem. 1999; 274(6):3667-71. DOI: 10.1074/jbc.274.6.3667. View

13.

Visscher K, Block S . Versatile optical traps with feedback control. Methods Enzymol. 1998; 298:460-89. DOI: 10.1016/s0076-6879(98)98040-5. View

14.

Vale R, Fletterick R . The design plan of kinesin motors. Annu Rev Cell Dev Biol. 1997; 13:745-77. DOI: 10.1146/annurev.cellbio.13.1.745. View

15.

Kojima H, Muto E, Higuchi H, Yanagida T . Mechanics of single kinesin molecules measured by optical trapping nanometry. Biophys J. 1997; 73(4):2012-22. PMC: 1181101. DOI: 10.1016/S0006-3495(97)78231-6. View

16.

Hua W, Young E, Fleming M, Gelles J . Coupling of kinesin steps to ATP hydrolysis. Nature. 1997; 388(6640):390-3. DOI: 10.1038/41118. View

17.

Li Y, Brown J, Reshetnikova L, Blazsek A, Farkas L, Nyitray L . Visualization of an unstable coiled coil from the scallop myosin rod. Nature. 2003; 424(6946):341-5. DOI: 10.1038/nature01801. View

18.

Tripet B, Vale R, Hodges R . Demonstration of coiled-coil interactions within the kinesin neck region using synthetic peptides. Implications for motor activity. J Biol Chem. 1997; 272(14):8946-56. DOI: 10.1074/jbc.272.14.8946. View

19.

Howard J . The movement of kinesin along microtubules. Annu Rev Physiol. 1996; 58:703-29. DOI: 10.1146/annurev.ph.58.030196.003415. View

20.

Svoboda K, Mitra P, Block S . Fluctuation analysis of kinesin movement. Biophys J. 1995; 68(4 Suppl):69S. PMC: 1281870. View