MOLECULAR BASIS FOR CLATHRIN SELF ASSEMBLY

细胞通过吸收大部分营养物质和毒素 受体介导的内吞作用，这是一个导致分选的过程 受体结合的货物进入单独的笼状蛋白包裹的囊泡中 从质膜上掐掉。笼状蛋白具有一种 不同寻常的三棱柱形状，使其可以形成格子或篮子， 在这种萌芽或挤压过程中导致膜曲率 进程。在质膜上组装网状蛋白的机制是 被认为涉及盐桥，而伪装的来自 自由漂浮的囊泡受Hsc70调控。最近，这些结构 解决了网状蛋白的腿近端结构域和末端结构域， 从而使人们能够深入了解网状蛋白组装的可能机制。 我们正在研究组装的pH依赖机制，使用 可能对盐分有贡献的残基的结构突变 桥联或金属离子连接；探索新的 发现了笼状蛋白重链重复序列(CHCR)十个螺旋组件 在笼蛋白分子内重复七次，包括通过 组件中近端腿-近端腿相互作用的区域； 以及，绘制了笼蛋白和AP-2适配器之间的相互作用图 其便于在生理pH下通过基于结构的组装 诱变。

Cells draw in most of their nutrients and toxins through receptor-mediated endocytosis, a process which results in sorting receptor-bound cargo into individual clathrin coated vesicles that pinch off from the plasma membrane. The clathrin protein has an unusual triskelion shape that allows it to form a lattice or basket, causing the membrane curvature during this budding or pinching process. The mechanism of clathrin assembly on the plasma membrane is thought to involve salt bridges, while the dissembly from the free-floating vesicle is regulated by Hsc70. Recently the structures of the proximal leg and terminal domain of clathrin were solved, allowing insights into the possible mechanisms of clathrin assembly. We are studying the mechanism of pH dependence of assembly, using structure-based mutagenesis of residues likely contributing to salt bridges or metal ion liganding; exploring the function of the newly discovered clathrin heavy chain repeat (CHCR) ten helix module which repeats seven times within the clathrin molecule, including through the region of proximal leg-proximal leg interaction in the assembly; and, mapping the interactions between clathrin and the AP-2 adaptor which facilitates assembly at physiological pH by structure-based mutagenesis.