Department of Biochemistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
Structure. 2012 Oct 10;20(10):1737-45. doi: 10.1016/j.str.2012.08.004. Epub 2012 Aug 30.
Plasma membrane repair involves the coordinated effort of proteins and the inner phospholipid surface to mend the rupture and return the cell back to homeostasis. Here, we present the three-dimensional structure of a multiprotein complex that includes S100A10, annexin A2, and AHNAK, which along with dysferlin, functions in muscle and cardiac tissue repair. The 3.5 Å resolution X-ray structure shows that a single region from the AHNAK C terminus is recruited by an S100A10-annexin A2 heterotetramer, forming an asymmetric ternary complex. The AHNAK peptide adopts a coil conformation that arches across the heterotetramer contacting both annexin A2 and S100A10 protomers with tight affinity (∼30 nM) and establishing a structural rationale whereby both S100A10 and annexin proteins are needed in AHNAK recruitment. The structure evokes a model whereby AHNAK is targeted to the membrane surface through sandwiching of the binding region between the S100A10/annexin A2 complex and the phospholipid membrane.
质膜修复涉及蛋白质和内磷脂表面的协调作用，以修复破裂并使细胞恢复到稳态。在这里，我们展示了一个包含 S100A10、膜联蛋白 A2 和 AHNAK 的多蛋白复合物的三维结构，该复合物与 dysferlin 一起在肌肉和心脏组织修复中发挥作用。3.5Å 分辨率的 X 射线结构表明，AHNAK C 端的单个区域被 S100A10-膜联蛋白 A2 异四聚体募集，形成不对称的三元复合物。AHNAK 肽采用卷曲构象，横跨异四聚体与膜联蛋白 A2 和 S100A10 原聚体接触，具有紧密的亲和力（约 30 nM），并建立了一种结构原理，即 AHNAK 募集需要 S100A10 和膜联蛋白蛋白。该结构引发了一种模型，即通过 S100A10/膜联蛋白 A2 复合物与磷脂膜之间的结合区域的三明治夹，将 AHNAK 靶向到膜表面。
