6TWU

MAGI1_2 complexed with a phosphomimetic 16E6 peptide

6TWU の概要

• エントリーDOI: 10.2210/pdb6twu/pdb
• 分子名称: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1,Annexin A2, Protein E6, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: phosphorylation, motif, pdz domain, peptide binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 98757.56

構造登録者

Gogl, G.,Cousido-Siah, A.,Trave, G. (登録日: 2020-01-13, 公開日: 2020-04-01, 最終更新日: 2024-01-24)

主引用文献

Gogl, G.,Jane, P.,Caillet-Saguy, C.,Kostmann, C.,Bich, G.,Cousido-Siah, A.,Nyitray, L.,Vincentelli, R.,Wolff, N.,Nomine, Y.,Sluchanko, N.N.,Trave, G.
Dual Specificity PDZ- and 14-3-3-Binding Motifs: A Structural and Interactomics Study.
Structure, 28:747-759.e3, 2020

PubMed Abstract: Protein-protein interaction motifs are often alterable by post-translational modifications. For example, 19% of predicted human PDZ domain-binding motifs (PBMs) have been experimentally proven to be phosphorylated, and up to 82% are theoretically phosphorylatable. Phosphorylation of PBMs may drastically rewire their interactomes, by altering their affinities for PDZ domains and 14-3-3 proteins. The effect of phosphorylation is often analyzed by performing "phosphomimetic" mutations. Here, we focused on the PBMs of HPV16-E6 viral oncoprotein and human RSK1 kinase. We measured the binding affinities of native, phosphorylated, and phosphomimetic variants of both PBMs toward the 266 human PDZ domains. We co-crystallized all the motif variants with a selected PDZ domain to characterize the structural consequence of the different modifications. Finally, we elucidated the structural basis of PBM capture by 14-3-3 proteins. This study provides novel atomic and interactomic insights into phosphorylatable dual specificity motifs and the differential effects of phosphorylation and phosphomimetic approaches.

PubMed: 32294469
DOI: 10.1016/j.str.2020.03.010

実験手法

X-RAY DIFFRACTION (2.4 Å)