Structural highlights
Function
[ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [TWF1_MOUSE] Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure of the actin-depolymerizing factor homology domain in complex with actin.,Paavilainen VO, Oksanen E, Goldman A, Lappalainen P J Cell Biol. 2008 Jul 14;182(1):51-9. PMID:18625842[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Beeler JF, Patel BK, Chedid M, LaRochelle WJ. Cloning and characterization of the mouse homolog of the human A6 gene. Gene. 1997 Jul 1;193(1):31-7. PMID:9249064
- ↑ Vartiainen M, Ojala PJ, Auvinen P, Peranen J, Lappalainen P. Mouse A6/twinfilin is an actin monomer-binding protein that localizes to the regions of rapid actin dynamics. Mol Cell Biol. 2000 Mar;20(5):1772-83. PMID:10669753
- ↑ Falck S, Paavilainen VO, Wear MA, Grossmann JG, Cooper JA, Lappalainen P. Biological role and structural mechanism of twinfilin-capping protein interaction. EMBO J. 2004 Aug 4;23(15):3010-9. Epub 2004 Jul 29. PMID:15282541 doi:http://dx.doi.org/10.1038/sj.emboj.7600310
- ↑ Helfer E, Nevalainen EM, Naumanen P, Romero S, Didry D, Pantaloni D, Lappalainen P, Carlier MF. Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility. EMBO J. 2006 Mar 22;25(6):1184-95. Epub 2006 Mar 2. PMID:16511569 doi:http://dx.doi.org/7601019
- ↑ Paavilainen VO, Oksanen E, Goldman A, Lappalainen P. Structure of the actin-depolymerizing factor homology domain in complex with actin. J Cell Biol. 2008 Jul 14;182(1):51-9. PMID:18625842 doi:10.1083/jcb.200803100
