Integrin modelling

integrin2.pngIntegrins play a central role in processes as diverse as cell adhesion, migration and apoptosis. Their malfunction leads to a range of diseases including autoimmunity and cancer. Integrins can form a range of different heterodimers featuring a large extracellular domain, a helical transmembrane region and a small intracellular domain. Binding of protein ligands to the intracellular or extracellular regions leads to large conformational changes allowing the cell to bind the extracellular matrix and sense its environment.  Our goal is to provide an atomistic view of integrin structure and dynamics upon binding, and new leads for the development of drugs targeting integrin-related diseases. Our specific aims are:

  • generate structural models of integrin dimeric variants consistent with available data
  • characterise integrin dynamics upon binding, and how this is affected by known mutations
  • study how glycosylation and metal ion binding affect integrin ligand binding
  • predict the arrangement of integrin oligomeric assemblies