2O26

Structure of a class III RTK signaling assembly

Summary for 2O26

• Entry DOI: 10.2210/pdb2o26/pdb
• Related: 2O27
• Descriptor: Kit ligand, Mast/stem cell growth factor receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: stem cell factor, receptor tyrosine kinase, class iii, receptor-ligand complex, growth factor, cytokine, 4-helix bundle, cytokine-signaling protein complex, cytokine/signaling protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 8
• Total formula weight: 199505.66

Authors

Liu, H.,Chen, X.,Focia, P.J.,He, X. (deposition date: 2006-11-29, release date: 2007-03-13, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)