3NJP

The Extracellular and Transmembrane Domain Interfaces in Epidermal Growth Factor Receptor Signaling

3NJP の概要

• エントリーDOI: 10.2210/pdb3njp/pdb
• 分子名称: Epidermal growth factor receptor, Epidermal growth factor, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: receptor tyrosine kinase, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 151812.47

構造登録者

Lu, C.,Mi, L.-Z.,Grey, M.J.,Zhu, J.,Graef, E.,Yokoyama, S.,Springer, T.A. (登録日: 2010-06-17, 公開日: 2010-10-13, 最終更新日: 2024-10-16)

主引用文献

Lu, C.,Mi, L.Z.,Grey, M.J.,Zhu, J.,Graef, E.,Yokoyama, S.,Springer, T.A.
Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor.
Mol.Cell.Biol., 30:5432-5443, 2010

PubMed Abstract: The mechanisms by which signals are transmitted across the plasma membrane to regulate signaling are largely unknown for receptors with single-pass transmembrane domains such as the epidermal growth factor receptor (EGFR). A crystal structure of the extracellular domain of EGFR dimerized by epidermal growth factor (EGF) reveals the extended, rod-like domain IV and a small, hydrophobic domain IV interface compatible with flexibility. The crystal structure and disulfide cross-linking suggest that the 7-residue linker between the extracellular and transmembrane domains is flexible. Disulfide cross-linking of the transmembrane domain shows that EGF stimulates only moderate association in the first two α-helical turns, in contrast to association throughout the membrane over five α-helical turns in glycophorin A and integrin. Furthermore, systematic mutagenesis to leucine and phenylalanine suggests that no specific transmembrane interfaces are required for EGFR kinase activation. These results suggest that linkage between ligand-induced dimerization and tyrosine kinase activation is much looser than was previously envisioned.

PubMed: 20837704
DOI: 10.1128/MCB.00742-10

実験手法

X-RAY DIFFRACTION (3.304 Å)