2KS1

Heterodimeric association of Transmembrane domains of ErbB1 and ErbB2 receptors Enabling Kinase Activation

2KS1 の概要

• エントリーDOI: 10.2210/pdb2ks1/pdb
• 関連するPDBエントリー: 2jwa
• 分子名称: Receptor tyrosine-protein kinase erbB-2, Epidermal growth factor receptor (2 entities in total)
• 機能のキーワード: erbb1, erbb2, transmembrane, heterodimer, complex, tyrosine kinase receptor, bicelles, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P04626; Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Cytoplasm. Isoform 3: Cytoplasm: P00533
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 9468.65

構造登録者

Mineev, K.S.,Bocharov, E.V.,Pustovalova, Y.E.,Bocharova, O.V.,Chupin, V.V.,Arseniev, A.S. (登録日: 2009-12-24, 公開日: 2010-06-09, 最終更新日: 2024-05-01)

主引用文献

Mineev, K.S.,Bocharov, E.V.,Pustovalova, Y.E.,Bocharova, O.V.,Chupin, V.V.,Arseniev, A.S.
Spatial Structure of the Transmembrane Domain Heterodimer of ErbB1 and ErbB2 Receptor Tyrosine Kinases
J.Mol.Biol., 2010

PubMed Abstract: Growth factor receptor tyrosine kinases of the ErbB family play a significant role in vital cellular processes and various cancers. During signal transduction across plasma membrane, ErbB receptors are involved in lateral homodimerization and heterodimerization with proper assembly of their extracellular single-span transmembrane (TM) and cytoplasmic domains. The ErbB1/ErbB2 heterodimer appears to be the strongest and most potent inducer of cellular transformation and mitogenic signaling compared to other ErbB homodimers and heterodimers. Spatial structure of the heterodimeric complex formed by TM domains of ErbB1 and ErbB2 receptors embedded into lipid bicelles was obtained by solution NMR. The ErbB1 and ErbB2 TM domains associate in a right-handed alpha-helical bundle through their N-terminal double GG4-like motif T(648)G(649)X(2)G(652)A(653) and glycine zipper motif T(652)X(3)S(656)X(3)G(660), respectively. The described heterodimer conformation is believed to support the juxtamembrane and kinase domain configuration corresponding to the receptor active state. The capability for multiple polar interactions, along with hydrogen bonding between TM segments, correlates with the observed highest affinity of the ErbB1/ErbB2 heterodimer, implying an important contribution of the TM helix-helix interaction to signal transduction.

PubMed: 20471394
DOI: 10.1016/j.jmb.2010.05.016

実験手法

SOLUTION NMR