Abstract：
The spectrin-based membrane skeleton is a ubiquitous membrane-associated two-dimensional cytoskeleton underneath the lipid membrane of metazoan cells. Mutations of skeleton proteins impair the mechanical strength and functions of the membrane, leading to several different types of human diseases. Here, we report the cryo-EM structures of the native spectrin-actin junctional complex (from porcine erythrocytes), which is a specialized short F-actin acting as the central organizational unit of the membrane skeleton. While an α-/β-adducin hetero-tetramer binds to the barbed end of F-actin as a flexible cap, tropomodulin and SH3BGRL2 together create an absolute cap at the pointed end. The junctional complex is strengthened by ring-like structures of dematin in the middle actin layers and by patterned periodic interactions with tropomyosin over its entire length. This work serves as a structural framework for understanding the assembly and dynamics of membrane skeleton and offers insights into mechanisms of various ubiquitous F-actin-binding factors in other F-actin systems.
摘要：
基于血影蛋白的膜骨架是在后生动物细胞的脂质膜下普遍存在的与膜相关的二维细胞骨架。骨架蛋白的突变会损害膜的机械强度和功能，导致几种不同类型的人类疾病。这里,我们报道了天然血影蛋白-肌动蛋白连接复合物（来自猪红细胞）的低温-EM结构，它是一种专门的短F-肌动蛋白，充当膜骨架的中心组织单元。虽然α-/β-内收蛋白异源四聚体作为柔性帽与F-肌动蛋白的倒钩端结合，Tropomodulin和SH3BGRL2一起在尖端创建一个绝对帽。连接复合物通过中间肌动蛋白层中dematin的环状结构以及在其整个长度上与原肌球蛋白的图案化周期性相互作用而得到加强。这项工作作为理解膜骨架的组装和动力学的结构框架，并提供了对其他F-肌动蛋白系统中各种普遍存在的F-肌动蛋白结合因子的机制的见解。
