Structure, domain organization, and different conformational states of stem cell factor-induced intact KIT dimers

Yarden Opatowsky, Irit Lax, Francisco Tomé, Franziska Bleichert, Vinzenz M. Unger, Joseph Schlessinger*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Using electron microscopy and fitting of crystal structures, we present the 3D reconstruction of ligand-induced dimers of intact receptor tyrosine kinase, KIT. We observe that KIT protomers form close contacts throughout the entire structure of ligand-bound receptor dimers, and that the dimeric receptors adopt multiple, defined conformational states. Interestingly, the homotypic interactions in the membrane proximal Ig-like domain of the extracellular region differ from those observed in the crystal structure of the unconstrained extracellular regions. We observe two prevalent conformations in which the tyrosine kinase domains interact asymmetrically. The asymmetric arrangement of the cytoplasmic regions may represent snapshots of molecular interactions occurring during trans autophosphorylation. Moreover, the asymmetric arrangements may facilitate specific intermolecular interactions necessary for trans phosphorylation of different KIT autophosphorylation sites that are required for stimulation of kinase activity and recruitment of signaling proteins by activated KIT.

Original languageEnglish (US)
Pages (from-to)1772-1777
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number5
DOIs
StatePublished - Feb 4 2014

Keywords

  • Cancer
  • Cell signaling
  • Receptor tyrosine kinases
  • Structural biology
  • Structure analysis

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Structure, domain organization, and different conformational states of stem cell factor-induced intact KIT dimers'. Together they form a unique fingerprint.

  • Cite this