1nql
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Epidermal growth factor (EGF) receptor is the prototype of the ErbB (HER) | + | 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== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Ferguson, K | + | [[Category: Ferguson, K M.]] |
| - | [[Category: Lemmon, M | + | [[Category: Lemmon, M A.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: auto-inhibition]] | [[Category: auto-inhibition]] | ||
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[[Category: tyrosine kinase]] | [[Category: tyrosine kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:08:58 2008'' |
Revision as of 12:08, 21 February 2008
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Structure of the extracellular domain of human epidermal growth factor (EGF) receptor in an inactive (low pH) complex with EGF.
Contents |
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 disease associated with this structure: Hypomagnesemia 4, renal OMIM:[131530]
About this Structure
1NQL is a Protein complex structure of sequences from Homo sapiens with 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 Thu Feb 21 14:08:58 2008
