THE CRYSTAL-STRUCTURE OF PLASMA GELSOLIN - IMPLICATIONS FOR ACTIN SEVERING, CAPPING, AND NUCLEATION

The structure of gelsolin has been determined by crystallography and c omprises six structurally related domains that, in a Ca2+-free environ ment, pack together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enabl e binding to occur. We propose that binding Ca2+ can release the conne ctions that join the N- and C-terminal halves of gelsolin, enabling ea ch half to bind actin relatively independently. Domain shifts are prop osed in response to Ca2+ as bases for models of how gelsolin acts to s ever, cap, or nucleate F-actin filaments. The structure also invites d iscussion of polyphosphoinositide binding to segment 2 and suggests ho w mutation at Asp-187 could initiate a series of events that lead to d eposition of amyloid plaques, as observed in victims of familial amylo idosis (Finnish type).