2gs2

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Revision as of 20:15, 12 November 2007

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spinqualitylabelsall models 2gs2, resolution 2.800Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of the active EGFR kinase domain

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Adenocarcinoma of lung, response to tyrosine kinase inhibitor in OMIM:[131550], Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in OMIM:[131550], Nonsmall cell lung cancer, susceptibility to OMIM:[131550]

About this Structure

2GS2 is a Single protein structure of sequence from Homo sapiens. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Full crystallographic information is available from OCA.

Reference

An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor., Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J, Cell. 2006 Jun 16;125(6):1137-49. PMID:16777603

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