Conversation between Associate Editor Alex Toker and corresponding author Ron Bose
March 3, 2014 — In Part Three of our series of the best articles of 2013 in the The Journal of Biological Chemistry, we hear a conversation between Alex Toker, a professor in the Department of Pathology at Beth Israel Deaconess Medical Center, and Ron Bose, a medical oncologist and assistant professor in the Division of Biological and Biomedical Sciences at Washington University in St. Louis. Bose is the corresponding author of the paper “Carboxyl Group Footprinting Mass Spectrometry and Molecular Dynamics Identify Key Interactions in the HER2-HER3 Receptor Tyrosine Kinase Interface. ” This paper was named the JBC’s Best Article of 2013 in the category of Signal Transduction. The paper provides the first structural characterization of HER2-HER3 heterodimers, which are part of the receptor family that is used in the development of targeted cancer therapies. Here, Bose talks about his more than 10 years of research in the study of tyrosine kinases. He also talks about where the research is going, the development of innovation where mass spectrometry is limited in the study of protein complexes that can’t be crystalized, and the power of interdisciplinary studies for graduate students in science.
Carboxyl Group Footprinting Mass Spectrometry and Molecular Dynamics Identify Key Interactions in the HER2-HER3 Receptor Tyrosine Kinase Interface
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.
Click here to read a transcript of this podcast interview.