6MTU

Crystal structure of human Scribble PDZ1:pMCC complex

6MTU の概要

• エントリーDOI: 10.2210/pdb6mtu/pdb
• 分子名称: Protein scribble homolog, Colorectal mutant cancer protein, DI(HYDROXYETHYL)ETHER, ... (7 entities in total)
• 機能のキーワード: cell polarity, mcc, pdz domain, phosphorylation, cell adhesion
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 28104.29

構造登録者

Caria, S.,Stewart, B.Z.,Humbert, P.O.,Kvansakul, M. (登録日: 2018-10-22, 公開日: 2019-08-14, 最終更新日: 2024-11-06)

主引用文献

Caria, S.,Stewart, B.Z.,Jin, R.,Smith, B.J.,Humbert, P.O.,Kvansakul, M.
Structural analysis of phosphorylation-associated interactions of human MCC with Scribble PDZ domains.
Febs J., 286:4910-4925, 2019

PubMed Abstract: Scribble is a crucial adaptor protein that plays a pivotal role during establishment and control of cell polarity, impacting many physiological processes ranging from cell migration to immunity and organization of tissue architecture. Scribble harbours a leucine-rich repeat domain and four PDZ domains that mediate most of Scribble's interactions with other proteins. It has become increasingly clear that post-translational modifications substantially impact Scribble-ligand interactions, with phosphorylation being a major modulator of binding to Scribble. To better understand how Scribble PDZ domains direct cell polarity signalling and how phosphorylation impacts this process, we investigated human Scribble interactions with MCC (Mutated in Colorectal Cancer). We systematically evaluated the ability of all four individual Scribble PDZ domains to bind the PDZ-binding motif (PBM) of MCC as well as MCC phosphorylated at the -1 Ser position. We show that Scribble PDZ1 and PDZ3 are the major interactors with MCC, and that modifications to Ser at the -1 position in the MCC PBM only has a minor effect on binding to Scribble PDZ domains. We then examined the structural basis for these observations by determining the crystal structures of Scribble PDZ1 domain bound to both the unphosphorylated MCC PBM as well as phosphorylated MCC. Our structures indicated that phospho-Ser at the -1 position in MCC is not involved in major contacts with Scribble PDZ1, and in conjunction with our affinity measurements suggest that the impact of phosphorylation at the -1 position of MCC must extend beyond a simple modulation of the affinity for Scribble PDZ domains.

PubMed: 31317644
DOI: 10.1111/febs.15002

実験手法

X-RAY DIFFRACTION (2.141 Å)