PDF(Pubmed)
Abstract：
Cytoplasmic dynein is a microtubule motor vital for cellular organization and division. It functions as a ~4-megadalton complex containing its cofactor dynactin and a cargo-specific coiled-coil adaptor. However, how dynein and dynactin recognize diverse adaptors, how they interact with each other during complex formation, and the role of critical regulators such as lissencephaly-1 (LIS1) protein (LIS1) remain unclear. In this study, we determined the cryo-electron microscopy structure of dynein-dynactin on microtubules with LIS1 and the lysosomal adaptor JIP3. This structure reveals the molecular basis of interactions occurring during dynein activation. We show how JIP3 activates dynein despite its atypical architecture. Unexpectedly, LIS1 binds dynactin\'s p150 subunit, tethering it along the length of dynein. Our data suggest that LIS1 and p150 constrain dynein-dynactin to ensure efficient complex formation.
摘要：
细胞质动力蛋白是一种对细胞组织和分裂至关重要的微管运动。它的功能是〜4-megadalton复合物，其中包含其辅因子dynactin和货物特异性卷曲螺旋适配器。然而,动力蛋白和动力蛋白如何识别不同的衔接子，它们在复杂形成过程中如何相互作用，和关键调节因子如间脑蛋白-1(LIS1)(LIS1)的作用仍不清楚。在这项研究中,我们用LIS1和溶酶体接头JIP3测定了微管上动力蛋白-动力蛋白的低温电子显微镜结构。该结构揭示了在动力蛋白激活过程中发生的相互作用的分子基础。我们展示了JIP3如何激活动力蛋白，尽管它的非典型结构。出乎意料的是,LIS1结合dynactin的p150亚基，沿着动力蛋白的长度束缚它。我们的数据表明LIS1和p150限制动力蛋白-动力蛋白以确保有效的复合物形成。
