Oral Presentation 2014 International Biophysics Congress

Insulin's interaction with its receptor - a complex choreography of conformational change (#30)

Mike C. Lawrence 1 , Yanwu Yang 2 , Nelson B. Phillips 3 , Brian J. Smith 4 , Satya P. Yadav 5 , Colin W. Ward 1 , Michael A. Weiss 6 , John G. Menting 1
  1. Walter + Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
  2. Department of Biochemistry, Case Western Reserve University, Cleveland, OH, USA
  3. Department of Biochemistry, Case Western Reserve University, Cleveland, OH, USA
  4. La Trobe University for Molecular Science, La Trobe University, Melbourne, VIC, Australia
  5. Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
  6. Departments of Biochemistry, Medicine and Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

The structural biology of the insulin - insulin receptor interaction has until very recently1 proved to be elusive. Here, we describe the changes that occur in both the hormone and the receptor upon insulin engaging its primary binding site on the receptor surface. In particular, we show that the hormone's B-chain C-terminal strand undergoes a hinge-like conformational change upon receptor engagement. In addition, we present data that suggest that this conformational change is integrally involved in protecting the hormone from inappropriate aggregation during its conformational life-cycle.

  1. Menting et al. (2013). Nature, 493, 241-5.