Institute of Molecular and Cell Biology, A*STAR, Proteos, Singapore.
Nat Struct Mol Biol. 2010 Apr;17(4):497-503. doi: 10.1038/nsmb.1792. Epub 2010 Mar 28.
Capping protein (CP) regulates actin dynamics by binding the barbed ends of actin filaments. Removal of CP may be one means to harness actin polymerization for processes such as cell movement and endocytosis. Here we structurally and biochemically investigated a CP interaction (CPI) motif present in the otherwise unrelated proteins CARMIL and CD2AP. The CPI motif wraps around the stalk of the mushroom-shaped CP at a site distant from the actin-binding interface, which lies on the top of the mushroom cap. We propose that the CPI motif may act as an allosteric modulator, restricting CP to a low-affinity, filament-binding conformation. Structure-based sequence alignments extend the CPI motif-containing family to include CIN85, CKIP-1, CapZIP and a relatively uncharacterized protein, WASHCAP (FAM21). Peptides comprising these CPI motifs are able to inhibit CP and to uncap CP-bound actin filaments.
衔接蛋白 (CP) 通过结合肌动蛋白丝的帽状末端来调节肌动蛋白的动态。去除 CP 可能是利用肌动蛋白聚合的一种手段，例如细胞运动和内吞作用。在这里，我们从结构和生化两方面研究了存在于不相关蛋白 CARMIL 和 CD2AP 中的 CP 相互作用 (CPI) 基序。CPI 基序缠绕在蘑菇形 CP 的柄上，位于远离肌动蛋白结合界面的位置，而肌动蛋白结合界面位于蘑菇帽的顶部。我们提出，CPI 基序可能作为一种变构调节剂，将 CP 限制在低亲和力、丝状结合构象。基于结构的序列比对将包含 CPI 基序的家族扩展到包括 CIN85、CKIP-1、CapZIP 和一个相对未被表征的蛋白 WASHCAP（FAM21）。包含这些 CPI 基序的肽能够抑制 CP 并解开 CP 结合的肌动蛋白丝。
