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Tytuł:
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Crystal structure of the FERM-folded talin head reveals the determinants for integrin binding.
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Autorzy:
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Pingfeng Zhang
Azizi, Latifeh
Kukkurainen, Sampo
Tong Gao
Mo Baikoghli
Jacquier, Marie-Claude
Yijuan Sun
Määttä, Juha A. E.
Cheng, R. Holland
Wehrle-Haller, Bernhard
Hytönen, Vesa P.
Jinhua Wu
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Temat:
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INTEGRINS
CRYSTAL structure
CELL adhesion
ADAPTOR proteins
MORPHOGENESIS
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Źródło:
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Proceedings of the National Academy of Sciences of the United States of America; 12/22/2020, Vol. 117 Issue 51, p32402-32412, 11p
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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 β3-integrin binding. Here, we present a crystal structure of a full-length talin head in complex with the β3-integrin tail. The structure reveals a compact FERM-like conformation and a tightly associated N-P-L-Y motif of β3-integrin. A critical C-terminal poly-lysine motif mediates FERM interdomain contacts and assures the tight association with the β3-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. [ABSTRACT FROM AUTHOR]
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