Abstract
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.
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Dates
Type | When |
---|---|
Created | 17 years, 1 month ago (July 14, 2008, 11:23 p.m.) |
Deposited | 2 years, 1 month ago (July 21, 2023, 10:41 p.m.) |
Indexed | 1 month, 1 week ago (July 26, 2025, 5:35 a.m.) |
Issued | 17 years, 1 month ago (July 14, 2008) |
Published | 17 years, 1 month ago (July 14, 2008) |
Published Online | 17 years, 1 month ago (July 14, 2008) |
Published Print | 17 years, 1 month ago (July 14, 2008) |
@article{Paavilainen_2008, title={Structure of the actin-depolymerizing factor homology domain in complex with actin}, volume={182}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200803100}, DOI={10.1083/jcb.200803100}, number={1}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Paavilainen, Ville O. and Oksanen, Esko and Goldman, Adrian and Lappalainen, Pekka}, year={2008}, month=jul, pages={51–59} }