Barrie Kyle R, Rebowski Grzegorz, Dominguez Roberto
Department of Physiology and Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nat Struct Mol Biol. 2025 Feb;32(2):237-242. doi: 10.1038/s41594-024-01412-5. Epub 2024 Oct 24.
Gelsolin is the prototypical member of a family of Ca-activated F-actin severing and capping proteins. Here we report structures of Ca-bound human gelsolin at the barbed end of F-actin. One structure reveals gelsolin's six domains (G1G6) and interdomain linkers wrapping around F-actin, while another shows domains G1G3-a fragment observed during apoptosis-binding on both sides of F-actin. Conformational changes that trigger severing occur on one side of F-actin with G1G6 and on both sides with G1G3. Gelsolin remains bound after severing, blocking subunit exchange.
凝溶胶蛋白是钙激活的F-肌动蛋白切断和封端蛋白家族的典型成员。在此,我们报告了结合钙的人凝溶胶蛋白在F-肌动蛋白尖端的结构。一种结构显示凝溶胶蛋白的六个结构域(G1-G6)和结构域间连接子环绕在F-肌动蛋白周围,而另一种结构显示结构域G1-G3——在细胞凋亡期间观察到的一个片段——结合在F-肌动蛋白的两侧。触发切断的构象变化发生在F-肌动蛋白的一侧(与G1-G6相关)以及两侧(与G1-G3相关)。切断后凝溶胶蛋白仍保持结合状态,阻止亚基交换。