2MEU

NMR spatial structure of mutant dimeric TM domain of VEGFR2 receptor

2MEU の概要

• エントリーDOI: 10.2210/pdb2meu/pdb
• 関連するPDBエントリー: 2MET
• NMR情報: BMRB: 19532
• 分子名称: Vascular endothelial growth factor receptor 2 (1 entity in total)
• 機能のキーワード: vegfr2, receptor tyrosine kinase, homodimer, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell junction . Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted . Isoform 3: Secreted: P35968
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 8370.14

構造登録者

Mineev, K.S.,Arseniev, A.S.,Lyukmanova, E.N.,Shulepko, M.A.,Kirpichnikov, M.P. (登録日: 2013-10-02, 公開日: 2014-07-30, 最終更新日: 2024-05-15)

主引用文献

Manni, S.,Mineev, K.S.,Usmanova, D.,Lyukmanova, E.N.,Shulepko, M.A.,Kirpichnikov, M.P.,Winter, J.,Matkovic, M.,Deupi, X.,Arseniev, A.S.,Ballmer-Hofer, K.
Structural and functional characterization of alternative transmembrane domain conformations in VEGF receptor 2 activation
Structure, 22:1077-1089, 2014

PubMed Abstract: Transmembrane signaling by receptor tyrosine kinases (RTKs) entails ligand-mediated dimerization and structural rearrangement of the extracellular domains. RTK activation also depends on the specific orientation of the transmembrane domain (TMD) helices, as suggested by pathogenic, constitutively active RTK mutants. Such mutant TMDs carry polar amino acids promoting stable transmembrane helix dimerization, which is essential for kinase activation. We investigated the effect of polar amino acids introduced into the TMD of vascular endothelial growth factor receptor 2, regulating blood vessel homeostasis. Two mutants showed constitutive kinase activity, suggesting that precise TMD orientation is mandatory for kinase activation. Nuclear magnetic resonance spectroscopy revealed that TMD helices in activated constructs were rotated by 180° relative to the interface of the wild-type conformation, confirming that ligand-mediated receptor activation indeed results from transmembrane helix rearrangement. A molecular dynamics simulation confirmed the transmembrane helix arrangement of wild-type and mutant TMDs revealed by nuclear magnetic resonance spectroscopy.

PubMed: 24980797
DOI: 10.1016/j.str.2014.05.010

実験手法

SOLUTION NMR