2GS7

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

Summary for 2GS7

• Entry DOI: 10.2210/pdb2gs7/pdb
• Related: 2GS2 2GS6
• Descriptor: Epidermal growth factor receptor, MAGNESIUM ION, IODIDE ION, ... (5 entities in total)
• Functional Keywords: egfr, kinase, inactive, amp-pnp, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• Total number of polymer chains: 2
• Total formula weight: 77699.99

Authors

Zhang, X.,Gureasko, J.,Shen, K.,Cole, P.A.,Kuriyan, J. (deposition date: 2006-04-25, release date: 2006-06-20, Last modification date: 2023-08-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)