2N2A

Spatial structure of HER2/ErbB2 dimeric transmembrane domain in the presence of cytoplasmic juxtamembrane domains

2N2A の概要

• エントリーDOI: 10.2210/pdb2n2a/pdb
• NMR情報: BMRB: 25593
• 分子名称: Receptor tyrosine-protein kinase erbB-2 (1 entity in total)
• 機能のキーワード: her2, erbb2, tyrosine kinase, activation, transmembrane, membrane protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Cytoplasm. Isoform 3: Cytoplasm: P04626
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13019.72

構造登録者

Bragin, P.E.,Mineev, K.S.,Bocharov, E.,Bocharova, O.,Arseniev, A. (登録日: 2015-05-05, 公開日: 2016-02-24, 最終更新日: 2024-05-15)

主引用文献

Bragin, P.E.,Mineev, K.S.,Bocharova, O.V.,Volynsky, P.E.,Bocharov, E.V.,Arseniev, A.S.
HER2 Transmembrane Domain Dimerization Coupled with Self-Association of Membrane-Embedded Cytoplasmic Juxtamembrane Regions.
J.Mol.Biol., 428:52-61, 2016

PubMed Abstract: Receptor tyrosine kinases of the human epidermal growth factor receptor (HER or ErbB) family transduce biochemical signals across plasma membrane, playing a significant role in vital cellular processes and in various cancers. Inactive HER/ErbB receptors exist in equilibrium between the monomeric and unspecified pre-dimerized states. After ligand binding, the receptors are involved in strong lateral dimerization with proper assembly of their extracellular ligand-binding, single-span transmembrane, and cytoplasmic kinase domains. The dimeric conformation of the HER2 transmembrane domain that is believed to support the cytoplasmic kinase domain configuration corresponding to the receptor active state was previously described in lipid bicelles. Here we used high-resolution NMR spectroscopy in another membrane-mimicking micellar environment and identified an alternative HER2 transmembrane domain dimerization coupled with self-association of membrane-embedded cytoplasmic juxtamembrane region. Such a dimerization mode appears to be capable of effectively inhibiting the receptor kinase activity. This finding refines the molecular mechanism regarding the signal propagation steps from the extracellular to cytoplasmic domains of HER/ErbB receptors.

PubMed: 26585403
DOI: 10.1016/j.jmb.2015.11.007

実験手法

SOLUTION NMR