2GS7

Crystal Structure of the inactive EGFR kinase domain in complex with AMP-PNP

2GS7 の概要

• エントリーDOI: 10.2210/pdb2gs7/pdb
• 関連するPDBエントリー: 2GS2 2GS6
• 分子名称: Epidermal growth factor receptor, MAGNESIUM ION, IODIDE ION, ... (5 entities in total)
• 機能のキーワード: egfr, kinase, inactive, amp-pnp, 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: 77699.99

構造登録者

Zhang, X.,Gureasko, J.,Shen, K.,Cole, P.A.,Kuriyan, J. (登録日: 2006-04-25, 公開日: 2006-06-20, 最終更新日: 2023-08-30)

主引用文献

Zhang, X.,Gureasko, J.,Shen, K.,Cole, P.A.,Kuriyan, J.
An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor
Cell(Cambridge,Mass.), 125:1137-1149, 2006

PubMed Abstract: The mechanism by which the epidermal growth factor receptor (EGFR) is activated upon dimerization has eluded definition. We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation. This suggests that the kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation. Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin-dependent kinases (CDKs). EGFR activation results from the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes. The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization.

PubMed: 16777603
DOI: 10.1016/j.cell.2006.05.013

実験手法

X-RAY DIFFRACTION (2.6 Å)