The Crystal Structure of Plasma Gelsolin: Implications for Actin Severing, Capping, and Nucleation

• Published in: Cell Vol. 90; no. 4; pp. 661 - 670
• Main Authors: Burtnick, Leslie D., Koepf, Edward K., Grimes, Jonathan, Jones, E.Yvonne, Stuart, David I., McLaughlin, Paul J., Robinson, Robert C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.08.1997
• Subjects: Actins - metabolism; Amino Acid Sequence; Animals; Calcium - metabolism; Crystallography, X-Ray; Gelsolin - blood; Gelsolin - chemistry; Horses; Models, Molecular; Molecular Sequence Data; Protein Conformation; Sequence Alignment
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80527-9

The structure of gelsolin has been determined by crystallography and comprises six structurally related domains that, in a Ca2+-free environment, pack together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur. We propose that binding Ca2+ can release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently. Domain shifts are proposed in response to Ca2+ as bases for models of how gelsolin acts to sever, cap, or nucleate F-actin filaments. The structure also invites discussion of polyphosphoinositide binding to segment 2 and suggests how mutation at Asp-187 could initiate a series of events that lead to deposition of amyloid plaques, as observed in victims of familial amyloidosis (Finnish type).