4WSI

Crystal Structure of PALS1/Crb complex

4WSI の概要

• エントリーDOI: 10.2210/pdb4wsi/pdb
• 分子名称: MAGUK p55 subfamily member 5, Protein crumbs (3 entities in total)
• 機能のキーワード: supramodule, peptide binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell membrane; Peripheral membrane protein: Q8N3R9; Apical cell membrane ; Single- pass type I membrane protein : P10040
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 99438.09

構造登録者

Wei, Z.,Li, Y.,Zhang, M. (登録日: 2014-10-28, 公開日: 2014-11-26, 最終更新日: 2024-03-20)

主引用文献

Li, Y.,Wei, Z.,Yan, Y.,Wan, Q.,Du, Q.,Zhang, M.
Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex.
Proc.Natl.Acad.Sci.USA, 111:17444-17449, 2014

PubMed Abstract: The Crumbs (Crb) complex, formed by Crb, PALS1, and PATJ, is evolutionarily conserved in metazoans and acts as a master cell-growth and -polarity regulator at the apical membranes in polarized epithelia. Crb intracellular functions, including its direct binding to PALS1, are mediated by Crb's highly conserved 37-residue cytoplasmic tail. However, the mechanistic basis governing the highly specific Crb-PALS1 complex formation is unclear, as reported interaction between the Crb tail (Crb-CT) and PALS1 PSD-95/DLG/ZO-1 (PDZ) domain is weak and promiscuous. Here we have discovered that the PDZ-Src homolgy 3 (SH3)-Guanylate kinase (GK) tandem of PALS1 binds to Crb-CT with a dissociation constant of 70 nM, which is ∼ 100-fold stronger than the PALS1 PDZ-Crb-CT interaction. The crystal structure of the PALS1 PDZ-SH3-GK-Crb-CT complex reveals that PDZ-SH3-GK forms a structural supramodule with all three domains contributing to the tight binding to Crb. Mutations disrupting the tertiary interactions of the PDZ-SH3-GK supramodule weaken the PALS1-Crb interaction and compromise PALS1-mediated polarity establishment in Madin-Darby canine kidney (MDCK) cysts. We further show that specific target binding of other members of membrane-associated guanylate kinases (MAGUKs) (e.g., CASK binding to neurexin) also requires the presence of their PDZ-SH3-GK tandems.

PubMed: 25385611
DOI: 10.1073/pnas.1416515111

実験手法

X-RAY DIFFRACTION (2.95 Å)