2M0B

Homodimeric transmembrane domain of the human receptor tyrosine kinase ErbB1 (EGFR, HER1) in micelles

2M0B の概要

• エントリーDOI: 10.2210/pdb2m0b/pdb
• NMR情報: BMRB: 18804
• 分子名称: Epidermal growth factor receptor (1 entity in total)
• 機能のキーワード: transmembrane domain, erbb1, receptor, dimerization, tyrosine kinase, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 9467.70

構造登録者

Lesovoy, D.M.,Bocharov, E.V.,Pustovalova, Y.E.,Bocharova, O.V.,Arseniev, A.S. (登録日: 2012-10-24, 公開日: 2013-10-30, 最終更新日: 2024-05-01)

主引用文献

Bocharov, E.V.,Lesovoy, D.M.,Pavlov, K.V.,Pustovalova, Y.E.,Bocharova, O.V.,Arseniev, A.S.
Alternative packing of EGFR transmembrane domain suggests that protein-lipid interactions underlie signal conduction across membrane.
Biochim. Biophys. Acta, 1858:1254-1261, 2016

PubMed Abstract: The human epidermal growth factor receptor (EGFR) of HER/ErbB receptor tyrosine kinase family mediates a broad spectrum of cellular responses transducing biochemical signals via lateral dimerization in plasma membrane, while inactive receptors can exist in both monomeric and dimeric forms. Recently, the dimeric conformation of the helical single-span transmembrane domains of HER/ErbB employing the relatively polar N-terminal motifs in a fashion permitting proper kinase activation was experimentally determined. Here we describe the EGFR transmembrane domain dimerization via an alternative weakly polar C-terminal motif A(661)xxxG(665) presumably corresponding to the inactive receptor state. During association, the EGFR transmembrane helices undergo a structural adjustment with adaptation of inter-molecular polar and hydrophobic interactions depending upon the surrounding membrane properties that directly affect the transmembrane helix packing. This might imply that signal transduction through membrane and allosteric regulation are inclusively mediated by coupled protein-protein and protein-lipid interactions, elucidating paradoxically loose linkage between ligand binding and kinase activation.

PubMed: 26903218
DOI: 10.1016/j.bbamem.2016.02.023

実験手法

SOLUTION NMR