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2o27

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Revision as of 10:54, 21 November 2007 by OCA (Talk | contribs)
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2o27, resolution 2.20Å

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Structure of a class III RTK signaling assembly

Overview

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.

About this Structure

2O27 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases., Liu H, Chen X, Focia PJ, He X, EMBO J. 2007 Feb 7;26(3):891-901. Epub 2007 Jan 25. PMID:17255936

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