Yeast two-hybrid screening service Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on February 7, 2007, 10.1073/pnas.0610939104
PNAS | February 13, 2007 | vol. 104 | no. 7 | 2175-2180


This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supporting Information
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hyeon, C.
Right arrow Articles by Onuchic, J. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hyeon, C.
Right arrow Articles by Onuchic, J. N.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

PHYSICAL SCIENCES / BIOLOGICAL SCIENCES / PHYSICS / BIOPHYSICS
Internal strain regulates the nucleotide binding site of the kinesin leading head

Changbong Hyeon, and José N. Onuchic{dagger}

Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, CA 92093-0374

Contributed by José N. Onuchic, December 9, 2006 (received for review November 28, 2006)

In the presence of ATP, kinesin proceeds along the protofilament of microtubule by alternated binding of two motor domains on the tubulin binding sites. Because the processivity of kinesin is much higher than other motor proteins, it has been speculated that there exists a mechanism for allosteric regulation between the two monomers. Recent experiments suggest that ATP binding to the leading head (L) domain in kinesin is regulated by the rearward strain built on the neck-linker. We test this hypothesis by explicitly modeling a C{alpha}-based kinesin structure whose motor domains are bound on the tubulin binding sites. The equilibrium structures of kinesin on the microtubule show disordered and ordered neck-linker configurations for the L and trailing head, respectively. The comparison of the structures between the two heads shows that several native contacts present at the nucleotide binding site in the L are less intact than those in the binding site of the rear head. The network of native contacts obtained from this comparison provides the internal tension propagation pathway, which leads to the disruption of the nucleotide binding site in the L. Also, using an argument based on polymer theory, we estimate the internal tension built on the neck-linker to be f {approx} 12–15 pN. Both of these conclusions support the experimental hypothesis.

cracking | internal strain-induced regulation | microtubule | processivity

Author contributions: C.H. and J.N.O. designed research; C.H. performed research; C.H. and J.N.O. analyzed data; and C.H. and J.N.O. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0610939104/DC1.

{dagger}To whom correspondence should be addressed at: Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0374. E-mail: jonuchic{at}ucsd.edu

© 2007 by The National Academy of Sciences of the USA


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Hyeon and J. N. Onuchic
Mechanical control of the directional stepping dynamics of the kinesin motor
PNAS, October 30, 2007; 104(44): 17382 - 17387.
[Abstract] [Full Text] [PDF]