2EC8

Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit

2EC8 の概要

• エントリーDOI: 10.2210/pdb2ec8/pdb
• 関連するPDBエントリー: 1EXZ 2E9W
• 分子名称: Mast/stem cell growth factor receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: glycoprotein, receptor tyrosine kinase, growth factor cytokine, dimerization, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60160.47

構造登録者

Yuzawa, S.,Opatowsky, Y.,Zhang, Z.,Mandiyan, V.,Lax, I.,Schlessinger, J. (登録日: 2007-02-11, 公開日: 2007-08-07, 最終更新日: 2024-10-16)

主引用文献

Yuzawa, S.,Opatowsky, Y.,Zhang, Z.,Mandiyan, V.,Lax, I.,Schlessinger, J.
Structural Basis for Activation of the Receptor Tyrosine Kinase KIT by Stem Cell Factor
Cell(Cambridge,Mass.), 130:323-334, 2007

PubMed Abstract: Stem Cell Factor (SCF) initiates its multiple cellular responses by binding to the ectodomain of KIT, resulting in tyrosine kinase activation. We describe the crystal structure of the entire ectodomain of KIT before and after SCF stimulation. The structures show that KIT dimerization is driven by SCF binding whose sole role is to bring two KIT molecules together. Receptor dimerization is followed by conformational changes that enable lateral interactions between membrane proximal Ig-like domains D4 and D5 of two KIT molecules. Experiments with cultured cells show that KIT activation is compromised by point mutations in amino acids critical for D4-D4 interaction. Moreover, a variety of oncogenic mutations are mapped to the D5-D5 interface. Since key hallmarks of KIT structures, ligand-induced receptor dimerization, and the critical residues in the D4-D4 interface, are conserved in other receptors, the mechanism of KIT stimulation unveiled in this report may apply for other receptor activation.

PubMed: 17662946
DOI: 10.1016/j.cell.2007.05.055

実験手法

X-RAY DIFFRACTION (3 Å)