Burtnick L D, Koepf E K, Grimes J, Jones E Y, Stuart D I, McLaughlin P J, Robinson R C
Department of Chemistry, University of British Columbia, Vancouver, Canada.
Cell. 1997 Aug 22;90(4):661-70. 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).
凝溶胶蛋白的结构已通过晶体学确定，它由六个结构相关的结构域组成，在无Ca2+的环境中，这些结构域聚集在一起形成紧密的球状结构，其中假定的肌动蛋白结合序列没有充分暴露以实现结合。我们提出，结合Ca2+可以释放连接凝溶胶蛋白N端和C端两半的连接，使每一半能够相对独立地结合肌动蛋白。响应Ca2+提出了结构域移位，作为凝溶胶蛋白如何切割、封端或成核F-肌动蛋白丝的模型基础。该结构还引发了关于多磷酸肌醇与第2节段结合的讨论，并提出了Asp-187处的突变如何引发一系列导致淀粉样斑块沉积的事件，如在家族性淀粉样变性（芬兰型）患者中观察到的那样。
