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Zhang P , Azizi L , Kukkurainen S , Gao T , Baikoghli M , Jacquier MC , Sun Y , Maatta JAE , Cheng RH , Wehrle-Haller B , Hytonen VP , Wu J
Crystal structure of the FERM-folded talin head reveals the determinants for integrin binding
Proc Natl Acad Sci U S A. 2020 Dec 22;117(51) :32402-32412
PMID: 33288722    PMCID: PMC7768682    URL: https://www.ncbi.nlm.nih.gov/pubmed/33288722
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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 beta3-integrin binding. Here, we present a crystal structure of a full-length talin head in complex with the beta3-integrin tail. The structure reveals a compact FERM-like conformation and a tightly associated N-P-L-Y motif of beta3-integrin. A critical C-terminal poly-lysine motif mediates FERM interdomain contacts and assures the tight association with the beta3-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.
Notes
Zhang, Pingfeng Azizi, Latifeh Kukkurainen, Sampo Gao, Tong Baikoghli, Mo Jacquier, Marie-Claude Sun, Yijuan Maatta, Juha A E Cheng, R Holland Wehrle-Haller, Bernhard Hytonen, Vesa P Wu, Jinhua eng Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32402-32412. doi: 10.1073/pnas.2014583117. Epub 2020 Dec 7.