[ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [WASL_MOUSE] Involved in mitosis and cytokinesis, via its role in the regulation of actin polymerization (By similarity). Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex. Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression.[1]
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 filament nucleators initiate polymerization in cells in a regulated manner. The common architecture among these molecules consists of tandem WASP homology 2 domains (W domains) that recruit three to four actin subunits to form a polymerization nucleus. We describe a low-resolution crystal structure of an actin dimer assembled by tandem W domains, where the first W domain is cross-linked to Cys374 of the actin subunit bound to it, whereas the last W domain is followed by the C-terminal pointed end-capping helix of thymosin beta4. While the arrangement of actin subunits in the dimer resembles that of a long-pitch helix of the actin filament, important differences are observed. These differences result from steric hindrance of the W domain with intersubunit contacts in the actin filament. We also determined the structure of the first W domain of Vibrio parahaemolyticus VopL cross-linked to actin Cys374 and show it to be nearly identical with non-cross-linked W-Actin structures. This result validates the use of cross-linking as a tool for the study of actin nucleation complexes, whose natural tendency to polymerize interferes with most structural methods. Combined with a biochemical analysis of nucleation, the structures may explain why nucleators based on tandem W domains with short inter-W linkers have relatively weak activity, cannot stay bound to filaments after nucleation, and are unlikely to influence filament elongation. The findings may also explain why nucleation-promoting factors of the Arp2/3 complex, which are related to tandem-W-domain nucleators, are ejected from branch junctions after nucleation. We finally show that the simple addition of the C-terminal pointed end-capping helix of thymosin beta4 to tandem W domains can change their activity from actin filament nucleation to monomer sequestration.
Structure of a Longitudinal Actin Dimer Assembled by Tandem W Domains: Implications for Actin Filament Nucleation.,Rebowski G, Namgoong S, Boczkowska M, Leavis PC, Navaza J, Dominguez R J Mol Biol. 2010 Sep 6. PMID:20804767[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑Suetsugu S, Takenawa T. Translocation of N-WASP by nuclear localization and export signals into the nucleus modulates expression of HSP90. J Biol Chem. 2003 Oct 24;278(43):42515-23. Epub 2003 Jul 18. PMID:12871950 doi:https://dx.doi.org/10.1074/jbc.M302177200
↑Rebowski G, Namgoong S, Boczkowska M, Leavis PC, Navaza J, Dominguez R. Structure of a Longitudinal Actin Dimer Assembled by Tandem W Domains: Implications for Actin Filament Nucleation. J Mol Biol. 2010 Sep 6. PMID:20804767 doi:10.1016/j.jmb.2010.08.040
