7D6F

The crystal structure of ARMS-PBM/MAGI2-PDZ4

7D6F の概要

• エントリーDOI: 10.2210/pdb7d6f/pdb
• 分子名称: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2, Kinase D-interacting substrate of 220 kDa, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: pbm/pdz interaction, scaffold protein, synaptic polaricity, structural protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12812.48

構造登録者

Ye, J.,Zhang, Y.,Zhong, Z.,Wang, C. (登録日: 2020-09-30, 公開日: 2020-11-04, 最終更新日: 2023-11-29)

主引用文献

Zhang, Y.,Zhong, Z.,Ye, J.,Wang, C.
Crystal structure of the PDZ4 domain of MAGI2 in complex with PBM of ARMS reveals a canonical PDZ recognition mode.
Neurochem.Int., 149:105152-105152, 2021

PubMed Abstract: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) is a neuronal scaffold protein that plays critical roles at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins through its multiple protein-protein interaction domains, including six PDZ domains, two phosphoserine-phosphothreonine binding WW domains, and a guanylate kinase GK domain. Previous studies showed that MAGI2 participates in formation of tetrameric complexes with PDZ-GEF1, TrkA receptor, and ankyrin repeat-rich membrane spanning (ARMS) protein at late endosomes and is crucial for neurite outgrowth. However, the molecular mechanism governing the assembly of these complexes remains unknown. Here, we characterize the direct interaction between MAGI2 and ARMS through multiple biochemical assays. Moreover, our solved crystal structure of the truncated PDZ4/PBM (PDZ binding motifs) complex of MAGI2 and ARMS proteins (MAGI2-PDZ4/ARMS-PBM) reveals that the binding interface lies between the αB/βB groove from the PDZ4 of MAGI2 and the C-terminal PBM from ARMS. The structure reveals high similarity to others in this protein family where canonical PDZ/PBM interactions are observed. However, the conserved "GLGF" motif in the PSD-95-PDZ3 changes to "GFGF" in the MAGI2-PDZ4/ARMS-PBM complex. We further validated our crystal structure through serial mutagenesis assays. Taken together, our study provides the biochemical details and binding mechanisms that underpin the stabilization of the MAGI2-PDZ4/ARMS-PBM complex, thereby offering a biochemical and structural basis for further understanding of the functional roles of MAGI2, ARMS, PDZ-GEF1, and TrkA in forming the tetrameric receptor complex in neuronal signaling.

PubMed: 34371146
DOI: 10.1016/j.neuint.2021.105152

実験手法

X-RAY DIFFRACTION (3.001 Å)