5LV6

N-terminal motif dimerization of EGFR transmembrane domain in bicellar environment

5LV6 の概要

• エントリーDOI: 10.2210/pdb5lv6/pdb
• NMR情報: BMRB: 34040
• 分子名称: Epidermal growth factor receptor (1 entity in total)
• 機能のキーワード: epidermal growth factor receptor, bicelles, activation mechanism, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 9467.70

構造登録者

Bragin, P.,Bocharov, E.,Mineev, K.,Bocharova, O.,Arseniev, A. (登録日: 2016-09-12, 公開日: 2017-04-05, 最終更新日: 2024-06-19)

主引用文献

Bocharov, E.V.,Bragin, P.E.,Pavlov, K.V.,Bocharova, O.V.,Mineev, K.S.,Polyansky, A.A.,Volynsky, P.E.,Efremov, R.G.,Arseniev, A.S.
The Conformation of the Epidermal Growth Factor Receptor Transmembrane Domain Dimer Dynamically Adapts to the Local Membrane Environment.
Biochemistry, 56:1697-1705, 2017

PubMed Abstract: The epidermal growth factor receptor (EGFR) family is an important class of receptor tyrosine kinases, mediating a variety of cellular responses in normal biological processes and in pathological states of multicellular organisms. Different modes of dimerization of the human EGFR transmembrane domain (TMD) in different membrane mimetics recently prompted us to propose a novel signal transduction mechanism based on protein-lipid interaction. However, the experimental evidence for it was originally obtained with slightly different TMD fragments used in the two different mimetics, compromising the validity of the comparison. To eliminate ambiguity, we determined the nuclear magnetic resonance (NMR) structure of the bicelle-incorporated dimer of the EGFR TMD fragment identical to the one previously used in micelles. The NMR results augmented by molecular dynamics simulations confirm the mutual influence of the TMD and lipid environment, as is required for the proposed lipid-mediated activation mechanism. They also reveal the possible functional relevance of a subtle interplay between the concurrent processes in the lipid and protein during signal transduction.

PubMed: 28291355
DOI: 10.1021/acs.biochem.6b01085

実験手法

SOLUTION NMR