3GQL

Crystal Structure of activated receptor tyrosine kinase in complex with substrates

Summary for 3GQL

• Entry DOI: 10.2210/pdb3gql/pdb
• Related: 3GQI
• Descriptor: Basic fibroblast growth factor receptor 1, (E)-[4-(3,5-difluorophenyl)-3H-pyrrolo[2,3-b]pyridin-3-ylidene](3-methoxyphenyl)methanol (3 entities in total)
• Functional Keywords: phosphorylated kinase, activation, atp analog, atp-binding, craniosynostosis, disease mutation, disulfide bond, dwarfism, glycoprotein, heparin-binding, hypogonadotropic hypogonadism, immunoglobulin domain, kallmann syndrome, kinase, membrane, nucleotide-binding, phosphoprotein, receptor, transferase, transmembrane, tyrosine-protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: P11362
• Total number of polymer chains: 3
• Total formula weight: 112965.65

Authors

Bae, J.H.,Lew, E.D.,Yuzawa, S.,Tome, F.,Lax, I.,Schlessinger, J. (deposition date: 2009-03-24, release date: 2009-08-18, Last modification date: 2024-02-21)

Primary citation

Bae, J.H.,Lew, E.D.,Yuzawa, S.,Tome, F.,Lax, I.,Schlessinger, J.
The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.
Cell(Cambridge,Mass.), 138:514-524, 2009

PubMed Abstract: SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. However, the modest binding affinity of SH2 domains to pY containing peptides may not account for and likely represents an oversimplified mechanism for regulation of selectivity of signaling pathways in living cells. Here we describe the crystal structure of the activated tyrosine kinase domain of FGFR1 in complex with a phospholipase Cgamma fragment. The structural and biochemical data and experiments with cultured cells show that the selectivity of phospholipase Cgamma binding and signaling via activated FGFR1 are determined by interactions between a secondary binding site on an SH2 domain and a region in FGFR1 kinase domain in a phosphorylation independent manner. These experiments reveal a mechanism for how SH2 domain selectivity is regulated in vivo to mediate a specific cellular process.

PubMed: 19665973
DOI: 10.1016/j.cell.2009.05.028

Experimental method

X-RAY DIFFRACTION (2.8 Å)