Han Huijong, Kursula Petri
From the Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland, the German Electron Synchrotron (DESY), 22607 Hamburg, Germany, and.
From the Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland, the German Electron Synchrotron (DESY), 22607 Hamburg, Germany, and the Department of Chemistry, University of Hamburg, 22607 Hamburg, Germany
J Biol Chem. 2014 May 16;289(20):14121-31. doi: 10.1074/jbc.M114.554816. Epub 2014 Mar 27.
Periaxin (PRX) is an abundant protein in the peripheral nervous system, with an important role in myelination. PRX participates in large molecular complexes, most likely through the interactions of its N-terminal PSD-95/Discs-large/ZO-1 (PDZ)-like domain. We present the crystal structures of the PDZ-like domains from PRX and its homologue AHNAK nucleoprotein 2 (AHNAK2). The unique intertwined, domain-swapped dimers provide a structural basis for the homodimerization of both proteins. The core of the homodimer is formed by a 6-stranded antiparallel β sheet, with every other strand from a different chain. The AHNAK2 PDZ domain structure contains a bound class III ligand peptide. The binding pocket is preformed, and the peptide-PDZ interactions have unique aspects, including two salt bridges and weak recognition of the peptide C terminus. Tight homodimerization may be central to the scaffolding functions of PRX and AHNAK2 in molecular complexes linking the extracellular matrix to the cytoskeletal network.
外周蛋白（PRX）是外周神经系统中一种丰富的蛋白质，在髓鞘形成中起重要作用。PRX参与大分子复合物的形成，很可能是通过其N端类PSD-95/盘状大蛋白/ZO-1（PDZ）结构域的相互作用来实现的。我们展示了PRX及其同源物AHNAK核蛋白2（AHNAK2）的类PDZ结构域的晶体结构。独特的相互缠绕、结构域交换二聚体为这两种蛋白质的同型二聚化提供了结构基础。同型二聚体的核心由一个6股反平行β折叠片层构成，每隔一股来自不同的链。AHNAK2的PDZ结构域结构包含一个结合的III类配体肽。结合口袋预先形成，肽与PDZ的相互作用具有独特之处，包括两个盐桥以及对肽C末端的弱识别。紧密的同型二聚化可能是PRX和AHNAK2在将细胞外基质与细胞骨架网络连接起来的分子复合物中发挥支架功能的核心。
