7WFY

Crystal Structure of the VAV2 SH2 domain in complex with APP phosphorylated peptide

7WFY の概要

• エントリーDOI: 10.2210/pdb7wfy/pdb
• 分子名称: Guanine nucleotide exchange factor VAV2, Amyloid beta A4 protein-binding family B member 1 (protein) (3 entities in total)
• 機能のキーワード: complex, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14895.55

構造登録者

Zhang, Y.J.,Liu, Y.R.,Wu, B. (登録日: 2021-12-27, 公開日: 2022-12-07, 最終更新日: 2024-10-23)

主引用文献

Zhang, Y.,Yang, X.,Liu, Y.,Ge, L.,Wang, J.,Sun, X.,Wu, B.,Wang, J.
Vav2 is a novel APP-interacting protein that regulates APP protein level.
Sci Rep, 12:12752-12752, 2022

PubMed Abstract: Amyloid precursor protein (APP) is a transmembrane protein that plays critical role in the pathogenesis of Alzheimer's disease (AD). It is also involved in many types of cancers. Increasing evidence has shown that the tyrosine phosphorylation site Y682 in the intracellular tail of APP is crucial for APP function. Here, we report that Vav2, a guanine nucleotide exchange factor (GEF) for Rho family GTPase, is a novel interaction partner of APP. We found that Vav2-SH2 domain was able to bind directly to the Y682-phosphorylated intracellular tail of APP through isothermal titration calorimetry and NMR titrating experiments. The crystal structure of Vav2-SH2 in complex with an APP-derived phosphopeptide was determined to understand the structural basis of this recognition specificity. The interaction of APP and Vav2 in a full-length manner was further confirmed in cells by GST pull-down, co-immunoprecipitation and immunofluorescence staining experiments. In addition, we found overexpression of Vav2 could inhibit APP degradation and markedly increase the protein levels of APP and its cleavage productions in 20E2 cells, and this function of Vav2 required a functional SH2 domain.

PubMed: 35882892
DOI: 10.1038/s41598-022-16883-z

実験手法

X-RAY DIFFRACTION (2.449 Å)