The globular head domain of talin, a large multi-domain cytoplasmic protein. is required for inside-out activation of the integrins, a family of heterodimeric transmembrane cell adhesion molecules Talin head contains a FERM domain that is composed of F1, F2, and F3 subdomains A F0 subdomain is located N-terminus to F1 The F3 contains a canonical phosphotyrosine binding (PTB) fold that directly interacts with the membrane proximal NPxY/F motif in the integrin beta cytoplasmic tail This interaction is stabilized by the F2 that interacts with the lipid head-groups of the plasma membrane. In comparison to F2 and F3, the properties of the F0F1 remains poorly characterized Here, we showed that F0F1 is essential for talin-induced activation of integrin alpha L beta 2 (LFA-1). F0F1 has a high content of beta-sheet secondary structure. and it tends to homodimerize that may provide stability against proteolysis and chaotrope induced unfolding (c) 2009 Elsevier Inc All rights reserved