Talin and kindlin use integrin tail allostery and direct binding to activate integrins.
Nat Struct Mol Biol
; 30(12): 1913-1924, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-38087085
ABSTRACT
Integrin affinity regulation, also termed integrin activation, is essential for metazoan life. Although talin and kindlin binding to the ß-integrin cytoplasmic tail is indispensable for integrin activation, it is unknown how they achieve this function. By combining NMR, biochemistry and cell biology techniques, we found that talin and kindlin binding to the ß-tail can induce a conformational change that increases talin affinity and decreases kindlin affinity toward it. We also discovered that this asymmetric affinity regulation is accompanied by a direct interaction between talin and kindlin, which promotes simultaneous binding of talin and kindlin to ß-tails. Disrupting allosteric communication between the ß-tail-binding sites of talin and kindlin or their direct interaction in cells severely compromised integrin functions. These data show how talin and kindlin cooperate to generate a small but critical population of ternary talin-ß-integrin-kindlin complexes with high talin-integrin affinity and high dynamics.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Integrinas
/
Talina
Límite:
Animals
Idioma:
En
Revista:
Nat Struct Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania