Wu, J.

Integrins consists of 24 species with diverse tissue-expression profiles and distinct biological functions. The {beta} subunit of integrin interacts with the FERM-folded head domain of talin through an N-P-x-Y/F motif, triggering integrin activation. Although this motif is conserved across most integrin-{beta} subunits, the detailed molecular mechanisms governing the specific recognition of different integrin species by talin remains unclear. We determined the crystal structure of talin head in complex with the {beta}2-integrin tail. The structure reveals a two-mode configuration featuring a \"rocking\" motion of the talin head FERM domain when compared with the {beta}3-bound talin head, leading to distinct inter-subdomain interactions and binding affinities. Moreover, stabilizing of the C-terminal -helix of talin head leads to enhanced affinity to integrin and its activation, suggesting a seesaw model of talin that orchestrates its function in mediating integrin activation in a species-specific manner.