Crystal structure of the FERM-folded talin head reveals the determinants for integrin binding.

ABSTRACT: Binding of the intracellular adapter proteins talin and its cofactor, kindlin, to the integrin receptors induces integrin activation and clustering. These processes are essential for cell adhesion, migration, and organ development. Although the talin head, the integrin-binding segment in talin, possesses a typical FERM-domain sequence, a truncated form has been crystallized in an unexpected, elongated form. This form, however, lacks a C-terminal fragment and possesses reduced ?3-integrin binding. Here, we present a crystal structure of a full-length talin head in complex with the ?3-integrin tail. The structure reveals a compact FERM-like conformation and a tightly associated N-P-L-Y motif of ?3-integrin. A critical C-terminal poly-lysine motif mediates FERM interdomain contacts and assures the tight association with the ?3-integrin cytoplasmic segment. Removal of the poly-lysine motif or disrupting the FERM-folded configuration of the talin head significantly impairs integrin activation and clustering. Therefore, structural characterization of the FERM-folded active talin head provides fundamental understanding of the regulatory mechanism of integrin function.

SUBMITTER: Zhang P 

PROVIDER: S-EPMC7768682 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature