The crystal structure of plasma gelsolin: implications for actin severing, capping, and nucleation.
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).
Burtnick
L D
LD
Department of Chemistry, University of British Columbia, Vancouver, Canada.
Koepf
E K
EK
Grimes
J
J
Jones
E Y
EY
Stuart
D I
DI
McLaughlin
P J
PJ
Robinson
R C
RC
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018360:Crystallography, X-Ray; D018260:Gelsolin / Q000097:blood / Q000737:chemistry*; D006736:Horses; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment
D000199:Actins; D018260:Gelsolin; D002118:Calcium