MAGUK 介导的细胞连接复合体组织的机制。

Mechanisms of MAGUK-mediated cellular junctional complex organization.

机构信息

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

出版信息

Curr Opin Struct Biol. 2018 Feb;48:6-15. doi: 10.1016/j.sbi.2017.08.006. Epub 2017 Sep 14.

DOI:10.1016/j.sbi.2017.08.006

PMID:28917202

Abstract

Membrane-associated guanylate kinases (MAGUKs) are a family of scaffold proteins that are enriched in cellular junctions and essential for tissue development and homeostasis. Mutations of MAGUKs are linked to many human diseases including cancers, psychiatric disorders, and intellectual disabilities. MAGUKs share a common PDZ-SH3-GK tandem domain organization at the C-terminal end. In this review, we summarize the mechanistic basis governing target recognition and regulations of this binding by the PDZ-SH3-GK tandem of various MAGUKs. We also discuss recent discoveries showing unique folding features of MAGUK PDZ-SH3-GK tandems that facilitate ligand-induced oligomerization of MAGUKs and phase transition of MAGUK-assembled synaptic signaling complexes.

摘要

膜相关鸟苷酸激酶（MAGUKs）是一类富含细胞连接的支架蛋白，对于组织发育和稳态至关重要。MAGUK 的突变与许多人类疾病有关，包括癌症、精神障碍和智力残疾。MAGUKs 在 C 末端共享一个常见的 PDZ-SH3-GK 串联结构域组织。在这篇综述中，我们总结了 PDZ-SH3-GK 串联结构域调控各种 MAGUK 蛋白靶标识别的机制基础。我们还讨论了最近的发现，这些发现显示了 MAGUK PDZ-SH3-GK 串联的独特折叠特征，促进了 MAGUK 配体诱导寡聚化和 MAGUK 组装的突触信号复合物的相变。