Suppr超能文献

寡聚化的脂筏连接蛋白-α促进 ELKS 的液-液相分离,从而分隔突触前活性区蛋白。

Oligomerized liprin-α promotes phase separation of ELKS for compartmentalization of presynaptic active zone proteins.

机构信息

Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

出版信息

Cell Rep. 2021 Mar 23;34(12):108901. doi: 10.1016/j.celrep.2021.108901.

Abstract

Synaptic scaffold proteins (e.g., liprin-α, ELKS, RIM, and RIM-BP) orchestrate ion channels, receptors, and enzymes at presynaptic terminals to form active zones for neurotransmitter release. The underlying mechanism of the active zone assembly remains elusive. Here, we report that liprin-α proteins have the potential to oligomerize through the N-terminal coiled-coil region. Our structural and biochemical characterizations reveal that a gain-of-function mutation promotes the self-assembly of the coiled coils in liprin-α2 by disrupting intramolecular interactions and promoting intermolecular interactions. By enabling multivalent interactions with ELKS proteins, the oligomerized coiled-coil region of liprin-α2 enhances the phase separation of the ELKS N-terminal segment. We further show that liprin-α2, by regulating the interplay between two phase separations of ELKS and RIM/RIM-BP, controls the protein distributions. These results imply that the complicated protein-protein interactions allow liprin-α to function with the active zone scaffolds and compartmentalize protein assemblies to achieve comprehensive functions in the active zone.

摘要

突触支架蛋白(例如,liprin-α、ELKS、RIM 和 RIM-BP)在突触前末端协调离子通道、受体和酶,形成神经递质释放的活性区。活性区组装的潜在机制仍不清楚。在这里,我们报告 liprin-α 蛋白通过 N 端卷曲螺旋区具有形成寡聚体的潜力。我们的结构和生化特性表明,功能获得性突变通过破坏分子内相互作用并促进分子间相互作用来促进 liprin-α2 卷曲螺旋的自组装。通过与 ELKS 蛋白的多价相互作用,liprin-α2 的寡聚化卷曲螺旋区增强了 ELKS N 端片段的相分离。我们进一步表明,liprin-α2 通过调节 ELKS 和 RIM/RIM-BP 之间的两种相分离的相互作用,控制蛋白质的分布。这些结果表明,复杂的蛋白质-蛋白质相互作用允许 liprin-α 与活性区支架相互作用,并将蛋白质组装分隔开,以在活性区实现全面功能。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验