Title | The calcium activation of gelsolin: Insights from the 3 angstrom structure of the G4-G6/actin complex |
Publication Type | Journal Article |
Year of Publication | 2002 |
Authors | Choe, H, Burtnick, LD, Mejillano, M, Yin, HL, Robinson, RC, Choe, S |
Journal | Journal of Molecular Biology |
Volume | 324 |
Pagination | 691-702 |
Date Published | Dec |
Type of Article | Article |
ISBN Number | 0022-2836 |
Keywords | actin, ACTIVATION, ACTOPHORIN, BINDING DOMAIN, CA2+, calcium, CAPPING PROTEIN, F-ACTIN, FAMILIAL AMYLOIDOSIS, FINNISH TYPE, gelsolin, IDENTIFICATION, MECHANISM, PLASMA GELSOLIN, REGULATION, severing |
Abstract | Gelsolin participates in the reorganization of the actin cytoskeleton that is required during such phenomena as cell movement, cytokinesis, and apoptosis. It consists of six structurally similar domains, G1-G6, which are arranged at resting intracellular levels of calcium ion so as to obscure the three actin-binding surfaces. Elevation of Ca2+ concentrations releases latches within the constrained structure and produces large shifts in the relative positioning of the domains, permitting gelsolin to bind to and sever actin filaments. How Ca2+ is able to activate gelsolin has been a major question concerning the function of this protein. We present the improved structure of the C-terminal half of gelsolin bound to monomeric actin at 3.0 Angstrom resolution. Two classes of Ca2+-binding site are evident on gelsolin: type 1 sites share coordination of Ca2+ with actin, while type 2 sites are wholly contained within gelsolin. This structure of the complex reveals the locations of two novel metal ion-binding sites in domains G5 and G6, respectively. We identify both as type 2 sites. The absolute conservation of the type 2 calcium-ligating residues across the six,domains of gelsolin suggests that this site exists in each of the domains. In total, gelsolin has the potential to bind eight calcium ions, two type 1 and six type 2. The function of the type 2 sites is to facilitate structural rearrangements within gelsolin as part of the activation and actin-binding and severing processes. We propose the novel type 2 site in G6 to be the critical site that initiates overall activation of gelsolin by releasing the tail latch that locks calcium-free gelsolin in a conformation unable to bind actin. (C) 2002 Elsevier Science Ltd. All rights reserved. |
URL | <Go to ISI>://000179825300011 |
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