McGee A W, Dakoji S R, Olsen O, Bredt D S, Lim W A, Prehoda K E
Department of Physiology, University of California-San Francisco, San Francisco, CA 94143, USA.
Mol Cell. 2001 Dec;8(6):1291-301. doi: 10.1016/s1097-2765(01)00411-7.
Membrane-associated guanylate kinases (MAGUKs), such as PSD-95, are modular scaffolds that organize signaling complexes at synapses and other cell junctions. MAGUKs contain PDZ domains, which recruit signaling proteins, as well as a Src homology 3 (SH3) and a guanylate kinase-like (GK) domain, implicated in scaffold oligomerization. The crystal structure of the SH3-GK module from PSD-95 reveals that these domains form an integrated unit: the SH3 fold comprises noncontiguous sequence elements divided by a hinge region and the GK domain. These elements compose two subdomains that can assemble in either an intra- or intermolecular fashion to complete the SH3 fold. We propose a model for MAGUK oligomerization in which complementary SH3 subdomains associate by 3D domain swapping. This model provides a possible mechanism for ligand regulation of oligomerization.
膜相关鸟苷酸激酶（MAGUKs），如PSD - 95，是模块化支架，可在突触和其他细胞连接点组织信号复合物。MAGUKs包含PDZ结构域，其招募信号蛋白，以及一个Src同源3（SH3）结构域和一个鸟苷酸激酶样（GK）结构域，与支架寡聚化有关。PSD - 95的SH3 - GK模块的晶体结构表明，这些结构域形成一个整合单元：SH3折叠由被铰链区隔开的不连续序列元件以及GK结构域组成。这些元件组成两个亚结构域，它们可以以分子内或分子间方式组装以完成SH3折叠。我们提出了一个MAGUK寡聚化模型，其中互补的SH3亚结构域通过三维结构域交换相互关联。该模型为寡聚化的配体调节提供了一种可能的机制。
