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Cited by 243Microtubule and mitosis dynamicsProtein Structure and DynamicsForce Microscopy Techniques and Applications

Kinesin’s processivity results from mechanical and chemical coordination between the ATP hydrolysis cycles of the two motor domains

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Hancock, William O., Howard, Jonathon·1999·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.96.23.13147PMC PMC23915
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Abstract

Kinesin is a processive motor protein: A single molecule can walk continuously along a microtubule for several micrometers, taking hundreds of 8-nm steps without dissociating. To elucidate the biochemical and structural basis for processivity, we have engineered a heterodimeric one-headed kinesin and compared its biochemical properties to those of the wild-type two-headed molecule. Our construct retains the functionally important neck and tail domains and supports motility in high-density microtubule gliding assays, though it fails to move at the single-molecule level. We find that the ATPase rate of one-headed kinesin is 3–6 s −1 and that detachment from the microtubule occurs at a similar rate (3 s −1 ). This establishes that one-headed kinesin usually detaches once per ATP hydrolysis cycle. Furthermore, we identify the rate-limiting step in the one-headed hydrolysis cycle as detachment from the microtubule in the ADP⋅P i state. Because the ATPase and detachment rates are roughly an order of magnitude lower than the corresponding rates for two-headed kinesin, the detachment of one head in the homodimer (in the ADP⋅P i state) must be accelerated by the other head. We hypothesize that this results from internal strain generated when the second head binds. This idea accords with a hand-over-hand model for processivity in which the release of the trailing head is contingent on the binding of the forward head. These new results, together with previously published ones, allow us to propose a pathway that defines the chemical and mechanical cycle for two-headed kinesin.

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  • Allosteric communication between the two kinesin motor domains is mediated through the internal load generated when both heads attach to the microtubule.

    “Several lines of evidence suggest that this allosteric communication is mediated through the internal load generated when both heads attach to the microtubule”

    From Stepping and Stretching (2003) · cites this paper as [1]

  • Members of the kinesin family of molecular motors are capable of taking over 100 steps on their microtubule track without dissociating.

    “Members of the kinesin family of molecular motors are capable of taking over 100 steps on their microtubule track without dissociating”

    From Stepping and Stretching (2003) · cites this paper as [1]

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Research works printed but not linked: 39

  1. [1]Coy D L, Howard J. Curr Opin Neurobiol. 1994;4:662–667. doi: 10.1016/0959-4388(94)90007-8. [DOI] [PubMed] [Google Scholar] · DOI
  2. [2]Bloom G S, Endow S A. Protein Profile. 1995;2:1109–1171. [PubMed] [Google Scholar]
  3. [3]Hirokawa N. Science. 1998;279:519–526. doi: 10.1126/science.279.5350.519. [DOI] [PubMed] [Google Scholar] · DOI
  4. [4]Howard J, Hudspeth A J, Vale R D. Nature (London) 1989;342:154–158. doi: 10.1038/342154a0. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  5. [5]Block S M, Goldstein L S, Schnapp B J. Nature (London) 1990;348:348–352. doi: 10.1038/348348a0. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  6. [6]Vale R D, Funatsu T, Pierce D W, Romberg L, Harada Y, Yanagida T. Nature (London) 1996;380:451–453. doi: 10.1038/380451a0. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  7. [7]Romberg L, Pierce D W, Vale R D. J Cell Biol. 1998;140:1407–1416. doi: 10.1083/jcb.140.6.1407. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  8. [9]Kojima H, Muto E, Higuchi H, Yanagida T. Biophys J. 1997;73:2012–2022. doi: 10.1016/S0006-3495(97)78231-6. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  9. [10]Ray S, Meyhofer E, Milligan R A, Howard J. J Cell Biol. 1993;121:1083–1093. doi: 10.1083/jcb.121.5.1083. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  10. [12]Schnitzer M J, Block S M. Nature (London) 1997;388:386–390. doi: 10.1038/41111. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  11. [15]Svoboda K, Block S M. Cell. 1994;77:773–784. doi: 10.1016/0092-8674(94)90060-4. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  12. [16]Meyhofer E, Howard J. Proc Natl Acad Sci USA. 1995;92:574–578. doi: 10.1073/pnas.92.2.574. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  13. [17]Yang J T, Laymon R A, Goldstein L S. Cell. 1989;56:879–889. doi: 10.1016/0092-8674(89)90692-2. [DOI] [PubMed] [Google Scholar] · DOI
  14. [18]de Cuevas M, Tao T, Goldstein L S. J Cell Biol. 1992;116:957–965. doi: 10.1083/jcb.116.4.957. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  15. [19]Huang T G, Suhan J, Hackney D D. J Biol Chem. 1994;269:16502–16507. [PubMed] [Google Scholar]
  16. [20]Howard J. Annu Rev Physiol. 1996;58:703–729. doi: 10.1146/annurev.ph.58.030196.003415. [DOI] [PubMed] [Google Scholar] · DOI
  17. [21]Hancock W O, Howard J. J Cell Biol. 1998;140:1395–1405. doi: 10.1083/jcb.140.6.1395. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  18. [22]Berliner E, Young E C, Anderson K, Mahtani H K, Gelles J. Nature (London) 1995;373:718–721. doi: 10.1038/373718a0. [DOI] [PubMed] [Google Scholar] · DOI
  19. [23]Okada Y, Hirokawa N. Science. 1999;283:1152–1157. doi: 10.1126/science.283.5405.1152. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  20. [24]Inoue Y, Toyoshima Y Y, Iwane A H, Morimoto S, Higuchi H, Yanagida T. Proc Natl Acad Sci USA. 1997;94:7275–7280. doi: 10.1073/pnas.94.14.7275. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  21. [26]Ma Y Z, Taylor E W. J Biol Chem. 1997;272:724–730. doi: 10.1074/jbc.272.2.724. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  22. [27]Jiang W, Hackney D D. J Biol Chem. 1997;272:5616–5621. doi: 10.1074/jbc.272.9.5616. [DOI] [PubMed] [Google Scholar] · DOI
  23. [29]Moyer M L, Gilbert S P, Johnson K A. Biochemistry. 1998;37:800–813. doi: 10.1021/bi9711184. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  24. [31]Hackney D D, Levitt J D, Suhan J. J Biol Chem. 1992;267:8696–8701. [PubMed] [Google Scholar]
  25. [34]Ma Y Z, Taylor E W. Biochemistry. 1995;34:13233–13241. doi: 10.1021/bi00040a039. [DOI] [PubMed] [Google Scholar] · DOI
  26. [35]Romberg L, Vale R D. Nature (London) 1993;361:168–170. doi: 10.1038/361168a0. [DOI] [PubMed] [Google Scholar] · DOI
  27. [36]Cross R A. Curr Biol. 1997;7:R631–R633. doi: 10.1016/s0960-9822(06)00320-4. [DOI] [PubMed] [Google Scholar] · DOI
  28. [37]Cross, R. A., Crevel, I., Carter, N. J., Alonso, M. C., Hirose, K. & Amos, L. A. (1999) Proc. R. Soc. London Ser. B, in press. [DOI] [PMC free article] [PubMed]
  29. [38]Gilbert S P, Webb M R, Brune M, Johnson K A. Nature (London) 1995;373:671–676. doi: 10.1038/373671a0. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  30. [39]Crevel I M, Lockhart A, Cross R A. J Mol Biol. 1996;257:66–76. doi: 10.1006/jmbi.1996.0147. [DOI] [PubMed] [Google Scholar] · DOI
  31. [40]Yount R G, Lawson D, Rayment I. Biophys J. 1995;68:44S–47S. [PMC free article] [PubMed] [Google Scholar]
  32. [41]Hackney D D. Proc Natl Acad Sci USA. 1988;85:6314–6318. doi: 10.1073/pnas.85.17.6314. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  33. [44]Yang J T, Saxton W M, Stewart R J, Raff E C, Goldstein L S. Science. 1990;249:42–47. doi: 10.1126/science.2142332. [DOI] [PubMed] [Google Scholar] · DOI
  34. [45]Gittes F, Meyhofer E, Baek S, Howard J. Biophys J. 1996;70:418–429. doi: 10.1016/S0006-3495(96)79585-1. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  35. [46]Visscher K, Schnitzer M J, Block S M. Nature (London) 1999;400:184–189. doi: 10.1038/22146. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  36. [47]Hirose K, Lowe J, Alonso M, Cross R A, Amos L A. Mol Biol Cell. 1999;10:2063–2074. doi: 10.1091/mbc.10.6.2063. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  37. [48]Arnal I, Wade R H. Structure (London) 1998;6:33–38. doi: 10.1016/s0969-2126(98)00005-7. [DOI] [PubMed] [Google Scholar] · DOI
  38. [49]Hirose K, Lockhart A, Cross R A, Amos L A. Proc Natl Acad Sci USA. 1996;93:9539–9544. doi: 10.1073/pnas.93.18.9539. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  39. [50]Kozielski F, Arnal I, Wade R H. Curr Biol. 1998;8:191–198. doi: 10.1016/s0960-9822(98)70083-1. [DOI] [PubMed] [Google Scholar] · DOI

Cited by

Sorted by citations

Authors
Hancock, W. O., & Howard, J.
Affiliations
University of Washington (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1999-11-09
Volume
96
Issue
23
Pages
13147-13152
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.96.23.13147
PMC
PMC23915
OpenAlex
W2171884409
Cited by
243
References
12
Citations by year
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FWCI
4.49
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR40593, R37AR040593, R01AR040593)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
Keywords
kinesin, processivity, ATP hydrolysis cycle, microtubule gliding, detachment rate, rate-determining step, microtubule motor proteins
MeSH terms
Adenosine Diphosphate, Adenosine Triphosphate, Animals, Drosophila, Hydrolysis, Kinetics, Microtubules, Kinesins

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