Structural Diversity in Integrin/Talin Interactions

The adhesion of integrins to the extracellular matrix is regulated by binding of the cytoskeletal protein talin to the cytoplasmic tail of the beta-integrin subunit. Structural studies of this interaction have hitherto largely focused on the beta 3-integrin, one member of the large and diverse integrin family. Here, we employ NMR to probe interactions and dynamics, revealing marked structural diversity in the contacts between beta 1A, beta 1D, and beta 3 tails and the Talin1 and Talin2 isoforms. Coupled with analysis of recent structures of talin/beta tail complexes, these studies elucidate the thermodynamic determinants of this heterogeneity and explain why the Talin2/beta 1D isoforms, which are co-localized in striated muscle, form an unusually tight interaction. We also show that talin/integrin affinity can be enhanced 1000-fold by deleting two residues in the beta tail. Together, these studies illustrate how the integrin/talin interaction has been fine-tuned to meet varying biological requirements.