Molecular basis of β2 integrin activation by talin unveils subunit-specific mechanisms of integrin signaling

This is the authors' abstract. We don't add key points for this paper.

Integrins consist of 24 species, each with unique tissue expression profiles and distinct biological functions. The β subunit of integrin interacts with the FERM-folded head domain of talin through an NPxY/F motif, triggering integrin activation. Although this motif is conserved across most integrin-β subunits, the precise molecular mechanism governing talin's selective recognition of different integrin-β subunits remains unclear. We identify two distinct configurations of the talin head when interacting with β2 and β3 integrins, providing critical insights into subunit-specific recognition of integrins. Structural studies reveal that mutations at the subdomain interface of the talin head can shift its β2-bound configuration to a β3-bound configuration. This shift enhances β2-integrin affinity, leading to increased lymphocyte function-associated antigen-1 (LFA-1)-mediated natural killer cell activity. Together, our data elucidate the structural basis of talin's role in mediating integrin activation in a subunit-specific manner and advance our understanding of how talin may regulate diverse functions of various integrin species.