JCB logo
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1083/jcb.200803100
The Journal of Cell Biology, Vol. 182, No. 1, 51-59
The Rockefeller University Press, 0021-9525 $30.00
© Paavilainen et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3145K)
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 Paavilainen, V. O.
Right arrow Articles by Lappalainen, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Paavilainen, V. O.
Right arrow Articles by Lappalainen, P.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*Protein
*Structure*UniGene
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Report

Structure of the actin-depolymerizing factor homology domain in complex with actin



Ville O. Paavilainen1, Esko Oksanen2, Adrian Goldman2,3, and Pekka Lappalainen1

1 Program in Cellular Biotechnology and 2 Program in Structural Biology and Biophysics, Institute of Biotechnology, and 3 Neuroscience Center, University of Helsinki, Helsinki FIN-00014, Finland

Correspondence to Pekka Lappalainen: pekka.lappalainen{at}helsinki.fi

Actin dynamics provide the driving force for many cellular processes including motility and endocytosis. Among the central cytoskeletal regulators are actin-depolymerizing factor (ADF)/cofilin, which depolymerizes actin filaments, and twinfilin, which sequesters actin monomers and caps filament barbed ends. Both interact with actin through an ADF homology (ADF-H) domain, which is also found in several other actin-binding proteins. However, in the absence of an atomic structure for the ADF-H domain in complex with actin, the mechanism by which these proteins interact with actin has remained unknown. Here, we present the crystal structure of twinfilin's C-terminal ADF-H domain in complex with an actin monomer. This domain binds between actin subdomains 1 and 3 through an interface that is conserved among ADF-H domain proteins. Based on this structure, we suggest a mechanism by which ADF/cofilin and twinfilin inhibit nucleotide exchange of actin monomers and present a model for how ADF/cofilin induces filament depolymerization by weakening intrafilament interactions.

V.O. Paavilainen's present address is Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158.

Abbreviations used in this paper: ADF-H, actin-depolymerizing factor homology; NBD, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole; WH2, WASP homology 2.

© 2008 Paavilainen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



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