3KXX

Structure of the mutant Fibroblast Growth Factor receptor 1

3KXX の概要

• エントリーDOI: 10.2210/pdb3kxx/pdb
• 関連するPDBエントリー: 3KY2
• 分子名称: Basic fibroblast growth factor receptor 1 (1 entity in total)
• 機能のキーワード: kinase, rtk, interface, phosphorylation, alternative splicing, atp-binding, chromosomal rearrangement, craniosynostosis, disease mutation, disulfide bond, dwarfism, glycoprotein, heparin-binding, hypogonadotropic hypogonadism, immunoglobulin domain, kallmann syndrome, membrane, nucleotide-binding, phosphoprotein, polymorphism, receptor, transferase, transmembrane, tyrosine-protein kinase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P11362
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 144794.09

構造登録者

Bae, J.H.,Boggon, T.J.,Tome, F.,Mandiyan, V.,Lax, I.,Schlessinger, J. (登録日: 2009-12-04, 公開日: 2010-03-02, 最終更新日: 2023-09-06)

主引用文献

Bae, J.H.,Boggon, T.J.,Tome, F.,Mandiyan, V.,Lax, I.,Schlessinger, J.
Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells.
Proc.Natl.Acad.Sci.USA, 107:2866-2871, 2010

PubMed Abstract: Tyrosine autophosphorylation of receptor tyrosine kinases plays a critical role in regulation of kinase activity and in recruitment and activation of intracellular signaling pathways. Autophosphorylation is mediated by a sequential and precisely ordered intermolecular (trans) reaction. In this report we present structural and biochemical experiments demonstrating that formation of an asymmetric dimer between activated FGFR1 kinase domains is required for transphosphorylation of FGFR1 in FGF-stimulated cells. Transphosphorylation is mediated by specific asymmetric contacts between the N-lobe of one kinase molecule, which serves as an active enzyme, and specific docking sites on the C-lobe of a second kinase molecule, which serves a substrate. Pathological loss-of-function mutations or oncogenic activating mutations in this interface may hinder or facilitate asymmetric dimer formation and transphosphorylation, respectively. The experiments presented in this report provide the molecular basis underlying the control of transphosphorylation of FGF receptors and other receptor tyrosine kinases.

PubMed: 20133753
DOI: 10.1073/pnas.0914157107

実験手法

X-RAY DIFFRACTION (3.2 Å)