| Structural highlights
6rsw is a 3 chain structure with sequence from Lk3 transgenic mice and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| NonStd Res: | |
| Related: | 6rsq |
| Gene: | Twf1, Ptk9 (LK3 transgenic mice), Cap1, Cap (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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. [CAP1_MOUSE] Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. [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]
Publication Abstract from PubMed
The ability of cells to generate forces through actin filament turnover was an early adaptation in evolution. While much is known about how actin filaments grow, mechanisms of their disassembly are incompletely understood. The best-characterized actin disassembly factors are the cofilin family proteins, which increase cytoskeletal dynamics by severing actin filaments. However, the mechanism by which severed actin filaments are recycled back to monomeric form has remained enigmatic. We report that cyclase-associated-protein (CAP) works in synergy with cofilin to accelerate actin filament depolymerization by nearly 100-fold. Structural work uncovers the molecular mechanism by which CAP interacts with actin filament pointed end to destabilize the interface between terminal actin subunits, and subsequently recycles the newly-depolymerized actin monomer for the next round of filament assembly. These findings establish CAP as a molecular machine promoting rapid actin filament depolymerization and monomer recycling, and explain why CAP is critical for actin-dependent processes in all eukaryotes.
Mechanism of synergistic actin filament pointed end depolymerization by cyclase-associated protein and cofilin.,Kotila T, Wioland H, Enkavi G, Kogan K, Vattulainen I, Jegou A, Romet-Lemonne G, Lappalainen P Nat Commun. 2019 Nov 22;10(1):5320. doi: 10.1038/s41467-019-13213-2. PMID:31757941[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Kotila T, Wioland H, Enkavi G, Kogan K, Vattulainen I, Jegou A, Romet-Lemonne G, Lappalainen P. Mechanism of synergistic actin filament pointed end depolymerization by cyclase-associated protein and cofilin. Nat Commun. 2019 Nov 22;10(1):5320. doi: 10.1038/s41467-019-13213-2. PMID:31757941 doi:http://dx.doi.org/10.1038/s41467-019-13213-2
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