2LNW

Identification and structural basis for a novel interaction between Vav2 and Arap3

2LNW の概要

• エントリーDOI: 10.2210/pdb2lnw/pdb
• 関連するPDBエントリー: 2LNX
• NMR情報: BMRB: 18182
• 分子名称: Guanine nucleotide exchange factor VAV2, Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 (2 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm (By similarity): Q8WWN8
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15758.57

構造登録者

Wu, B.,Zhang, J.,Wu, J.,Shi, Y. (登録日: 2012-01-05, 公開日: 2012-11-21, 最終更新日: 2024-10-16)

主引用文献

Wu, B.,Wang, F.,Zhang, J.,Zhang, Z.,Qin, L.,Peng, J.,Li, F.,Liu, J.,Lu, G.,Gong, Q.,Yao, X.,Wu, J.,Shi, Y.
Identification and structural basis for a novel interaction between Vav2 and Arap3.
J.Struct.Biol., 180:84-95, 2012

PubMed Abstract: Vav2 is a ubiquitous guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. It regulates processes including cell migration, neuronal development and phagocytosis through interactions with different proteins. In this study, Arap3, a dual GTPase-activating protein (GAP) for RhoA and Arf6, was first identified to be a novel interaction partner for Vav2 both in vitro and in vivo. ITC and NMR chemical shift perturbation experiments demonstrated that Vav2 SH2 domain was able to interact directly with phosphorylated Y1403 and Y1408 within the C-terminal region of Arap3 with high affinities, with the dissociation constants (Kd) of ≈ 0.27 and ≈ 1.40 μM, respectively. In addition, using different phosphotyrosine peptides, the pY +3 specificity of Vav2 SH2 domain was discovered. The solution structures of Vav2 SH2 domain in free and in complex with the phosphotyrosine peptide pY1408 were therefore determined to understand the structural basis of this recognition specificity. Structural analysis revealed that the presence of a Phe residue in the BG loop (BG6) leads to the formation of a shallow hydrophobic pY +3 pocket on the surface of Vav2 SH2 domain, which determines the pY +3 specificity of Vav2 SH2 domain.

PubMed: 22750419
DOI: 10.1016/j.jsb.2012.06.011

実験手法

SOLUTION NMR