JCB logo
MBoC5 from Garland Science
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 7 February 2005. doi:10.1083/jcb.200410114
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 4, 587-598
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 4391K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Slep, K. C.
Right arrow Articles by Vale, R. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Slep, K. C.
Right arrow Articles by Vale, R. D.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end

Kevin C. Slep1, Stephen L. Rogers1,2, Sarah L. Elliott3, Hiroyuki Ohkura3, Peter A. Kolodziej4, and Ronald D. Vale1,2

1 The Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94107
2 The Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94107
3 Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, The University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK
4 Department of Cell and Developmental Biology, Center for Molecular Neuroscience, Program in Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232

Correspondence to Ronald D. Vale: vale{at}cmp.ucsf.edu

EB1 is a member of a conserved protein family that localizes to growing microtubule plus ends. EB1 proteins also recruit cell polarity and signaling molecules to microtubule tips. However, the mechanism by which EB1 recognizes cargo is unknown. Here, we have defined a repeat sequence in adenomatous polyposis coli (APC) that binds to EB1's COOH-terminal domain and identified a similar sequence in members of the microtubule actin cross-linking factor (MACF) family of spectraplakins. We show that MACFs directly bind EB1 and exhibit EB1-dependent plus end tracking in vivo. To understand how EB1 recognizes APC and MACFs, we solved the crystal structure of the EB1 COOH-terminal domain. The structure reveals a novel homodimeric fold comprised of a coiled coil and four-helix bundle motif. Mutational analysis reveals that the cargo binding site for MACFs maps to a cluster of conserved residues at the junction between the coiled coil and four-helix bundle. These results provide a structural understanding of how EB1 binds two regulators of microtubule-based cell polarity.

Sarah L. Elliott's present address is Dept. of Biological Sciences, Stanford University, Stanford, CA 94305.

Abbreviations used in this paper: APC, adenomatous polyposis coli; ß-ME, ß-mercaptoethanol; MACF, microtubule actin cross-linking factor; MAD, multiwavelength anomalous diffraction; SeMet, selenomethionine.


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents