2O27

Structure of a class III RTK signaling assembly

2O27 の概要

• エントリーDOI: 10.2210/pdb2o27/pdb
• 関連するPDBエントリー: 2O26
• 分子名称: Kit ligand (2 entities in total)
• 機能のキーワード: stem cell factor, receptor tyrosine kinase, class iii, receptor-ligand complex, growth factor, cytokine, 4-helix bundle, signaling protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Isoform 1: Cell membrane; Single-pass type I membrane protein (By similarity). Isoform 2: Cell membrane; Single-pass type I membrane protein (By similarity). Soluble KIT ligand: Secreted (By similarity): P20826
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32889.53

構造登録者

Liu, H.,Chen, X.,Focia, P.,He, X. (登録日: 2006-11-29, 公開日: 2007-03-13, 最終更新日: 2024-10-16)

主引用文献

Liu, H.,Chen, X.,Focia, P.J.,He, X.
Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases.
Embo J., 26:891-901, 2007

PubMed Abstract: Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), to stimulate diverse processes including melanogenesis, gametogenesis and hematopoeisis. Dysregulation of KIT activation is associated with many cancers. We report a 2.5 A crystal structure of the functional core of SCF bound to the extracellular ligand-binding domains of KIT. The structure reveals a 'wrapping' SCF-recognition mode by KIT, in which KIT adopts a bent conformation to facilitate each of its first three immunoglobulin (Ig)-like domains to interact with SCF. Three surface epitopes on SCF, an extended loop, the B and C helices, and the N-terminal segment, contact distinct KIT domains, with two of the epitopes undergoing large conformational changes upon receptor binding. The SCF/KIT complex reveals a unique RTK dimerization assembly, and a novel recognition mode between four-helix bundle cytokines and Ig-family receptors. It serves as a framework for understanding the activation mechanisms of class III RTKs.

PubMed: 17255936
DOI: 10.1038/sj.emboj.7601545

実験手法

X-RAY DIFFRACTION (2.2 Å)