MOLECULAR BASIS FOR CLATHRIN SELF ASSEMBLY

网格蛋白自组装的分子基础

• 批准号: 6347980
• 负责人: DIANE E WAKEHAM
• 金额: $ 0.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6347980
• 关键词: biomedical resource; cardiovascular system; musculoskeletal system; nervous system

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.

细胞吸收大部分营养和毒素， 受体介导的内吞作用，这一过程导致 受体结合的货物进入单独的网格蛋白包被的囊泡， 从质膜上夹断。 网格蛋白具有 不寻常的三角形形状，使它能够形成一个格子或篮子， 在出芽或收缩期间引起膜弯曲 过程 网格蛋白在质膜上组装的机制是 被认为涉及盐桥，而从盐桥的 自由漂浮囊泡受Hsc 70调节。 最近，结构 网格蛋白的近端腿和末端结构域， 允许深入了解网格蛋白组装的可能机制。 我们正在研究组装的pH依赖性机制，使用 基于结构的突变可能有助于盐的残基 桥或金属离子配体;探索新的功能， 发现网格蛋白重链重复序列（CHCR）十螺旋模块， 在网格蛋白分子内重复七次，包括通过 组件中近端支腿-近端支腿相互作用的区域; 以及绘制网格蛋白和AP-2衔接子之间的相互作用 通过基于结构的方式促进在生理pH下的组装 诱变