1nql
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(New page: 200px<br /> <applet load="1nql" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nql, resolution 2.80Å" /> '''Structure of the ex...)
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Revision as of 16:17, 12 November 2007
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Structure of the extracellular domain of human epidermal growth factor (EGF) receptor in an inactive (low pH) complex with EGF.
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Overview
Epidermal growth factor (EGF) receptor is the prototype of the ErbB (HER), family receptor tyrosine kinases (RTKs), which regulate cell growth and, differentiation and are implicated in many human cancers. EGF activates, its receptor by inducing dimerization of the 621 amino acid EGF receptor, extracellular region. We describe the 2.8 A resolution crystal structure, of this entire extracellular region (sEGFR) in an unactivated state. The, structure reveals an autoinhibited configuration, where the dimerization, interface recently identified in activated sEGFR structures is completely, occluded by intramolecular interactions. To activate the receptor, EGF, binding must promote a large domain rearrangement that exposes this, dimerization interface. This contrasts starkly with other RTK activation, mechanisms and suggests new approaches for designing ErbB receptor, antagonists.
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
1NQL is a Protein complex structure of sequences from Homo sapiens with NAG as ligand. Full crystallographic information is available from OCA.
Reference
EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization., Ferguson KM, Berger MB, Mendrola JM, Cho HS, Leahy DJ, Lemmon MA, Mol Cell. 2003 Feb;11(2):507-17. PMID:12620237
Page seeded by OCA on Mon Nov 12 18:24:07 2007
