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 β-integrin subunit. Structural studies of this interaction have hitherto largely focused on the β3-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 β1A, β1D, and β3 tails and the Talin1 and Talin2 isoforms. Coupled with analysis of recent structures of talin/β tail complexes, these studies elucidate the thermodynamic determinants of this heterogeneity and explain why the Talin2/β1D 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 β tail. Together, these studies illustrate how the integrin/talin interaction has been fine-tuned to meet varying biological requirements.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX13DR, UK.
Nicholas J
NJ
Anthis
Kate L
KL
Wegener
David R
DR
Critchley
Iain D
ID
Campbell
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D006801:Humans; D019012:Integrin beta1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology; D025941:Protein Interaction Mapping; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D016608:Talin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D019012:Integrin beta1; D050505:Mutant Proteins; D020033:Protein Isoforms; C436513:TLN2 protein, human; D016608:Talin