Structural diversity in integrin/talin interactions.

ABSTRACT

The adhesion of integrins to the extracellular matrix is regulated by binding of the cytoskeletal protein talin to the cytoplasmic tail of the ß-integrin subunit. Structural studies of this interaction have hitherto largely focused on the ß3-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 ß1A, ß1D, and ß3 tails and the Talin1 and Talin2 isoforms. Coupled with analysis of recent structures of talin/ß tail complexes, these studies elucidate the thermodynamic determinants of this heterogeneity and explain why the Talin2/ß1D 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 ß tail. Together, these studies illustrate how the integrin/talin interaction has been fine-tuned to meet varying biological requirements.