Carboxyl group footprinting mass spectrometry and molecular dynamics identify key interactions in the HER2-HER3 receptor tyrosine kinase interface

Abstract

Background: HER2 and HER3 receptor tyrosine kinases form potent oncogenic signaling dimers. Results: Carboxyl group footprinting and molecular dynamics reveal changes in the HER2-HER3 dimer interface and the HER2 activation loop. Conclusion: HER2 and HER3 form asymmetric heterodimers in a single configuration. The HER2 unphosphorylated activation loop can assume an active conformation. Significance: This study provides the first structural characterization of HER2-HER3 kinase dimers. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.