3GT8

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

Summary for 3GT8

• Entry DOI: 10.2210/pdb3gt8/pdb
• Descriptor: Epidermal growth factor receptor, Unknown peptide, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: inactive kinase, dimer, alternative splicing, anti-oncogene, atp-binding, cell cycle, cell membrane, disease mutation, disulfide bond, glycoprotein, isopeptide bond, kinase, membrane, nucleotide-binding, phosphoprotein, polymorphism, receptor, secreted, transferase, transmembrane, tyrosine-protein kinase, ubl conjugation
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• Total number of polymer chains: 5
• Total formula weight: 153562.26

Authors

Jura, N.,Endres, N.F.,Engel, K.,Deindl, S.,Das, R.,Lamers, M.H.,Wemmer, D.E.,Zhang, X.,Kuriyan, J. (deposition date: 2009-03-27, release date: 2009-07-21, Last modification date: 2024-02-21)

Primary citation

Jura, N.,Endres, N.F.,Engel, K.,Deindl, S.,Das, R.,Lamers, M.H.,Wemmer, D.E.,Zhang, X.,Kuriyan, J.
Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment.
Cell(Cambridge,Mass.), 137:1293-1307, 2009

PubMed Abstract: Signaling by the epidermal growth factor receptor requires an allosteric interaction between the kinase domains of two receptors, whereby one activates the other. We show that the intracellular juxtamembrane segment of the receptor, known to potentiate kinase activity, is able to dimerize the kinase domains. The C-terminal half of the juxtamembrane segment latches the activated kinase domain to the activator, and the N-terminal half of this segment further potentiates dimerization, most likely by forming an antiparallel helical dimer that engages the transmembrane helices of the activated receptor. Our data are consistent with a mechanism in which the extracellular domains block the intrinsic ability of the transmembrane and cytoplasmic domains to dimerize and activate, with ligand binding releasing this block. The formation of the activating juxtamembrane latch is prevented by the C-terminal tails in a structure of an inactive kinase domain dimer, suggesting how alternative dimers can prevent ligand-independent activation.

PubMed: 19563760
DOI: 10.1016/j.cell.2009.04.025

Experimental method

X-RAY DIFFRACTION (2.955 Å)