4ZJV

crystal structure of EGFR kinase domain in complex with Mitogen-inducible gene 6 protein

4ZJV の概要

• エントリーDOI: 10.2210/pdb4zjv/pdb
• 関連するPDBエントリー: 4R3P 4R3R
• 分子名称: Epidermal growth factor receptor, ERBB receptor feedback inhibitor 1 (3 entities in total)
• 機能のキーワード: epidermal growth factor receptor (egfr), erbb receptor feedback inhibitor 1, mitogen-inducible gene 6 protein(mig6), transferase-inhibitor complex, transferase/inhibitor
• 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: P00533; Cytoplasm : Q9UJM3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 90880.29

構造登録者

Eck, M.J.,Park, E.,Lee, B. (登録日: 2015-04-29, 公開日: 2015-08-12, 最終更新日: 2023-11-15)

主引用文献

Park, E.,Kim, N.,Ficarro, S.B.,Zhang, Y.,Lee, B.I.,Cho, A.,Kim, K.,Park, A.K.,Park, W.Y.,Murray, B.,Meyerson, M.,Beroukhim, R.,Marto, J.A.,Cho, J.,Eck, M.J.
Structure and mechanism of activity-based inhibition of the EGF receptor by Mig6.
Nat.Struct.Mol.Biol., 22:703-711, 2015

PubMed Abstract: Mig6 is a feedback inhibitor that directly binds, inhibits and drives internalization of ErbB-family receptors. Mig6 selectively targets activated receptors. Here we found that the epidermal growth factor receptor (EGFR) phosphorylates Mig6 on Y394 and that this phosphorylation is primed by prior phosphorylation of an adjacent residue, Y395, by Src. Crystal structures of human EGFR-Mig6 complexes reveal the structural basis for enhanced phosphorylation of primed Mig6 and show how Mig6 rearranges after phosphorylation by EGFR to effectively irreversibly inhibit the same receptor that catalyzed its phosphorylation. This dual phosphorylation site allows Mig6 to inactivate EGFR in a manner that requires activation of the target receptor and that can be modulated by Src. Loss of Mig6 is a driving event in human cancer; analysis of 1,057 gliomas reveals frequent focal deletions of ERRFI1, the gene that encodes Mig6, in EGFR-amplified glioblastomas.

PubMed: 26280531
DOI: 10.1038/nsmb.3074

実験手法

X-RAY DIFFRACTION (2.7 Å)