PuSH - Publikationsserver des Helmholtz Zentrums München

Aretz, J.* ; Aziz, M. ; Strohmeyer, N.* ; Sattler, M. ; Fässler, R.*

Talin and kindlin use integrin tail allostery and direct binding to activate integrins.

Nat. Struct. Mol. Biol. 30, 1913-1924 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Integrin affinity regulation, also termed integrin activation, is essential for metazoan life. Although talin and kindlin binding to the β-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 β-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 β-tails. Disrupting allosteric communication between the β-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-β-integrin-kindlin complexes with high talin-integrin affinity and high dynamics.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Structural Basis; Adhesion Measurements; Domain; Complexes; Reveals
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Zeitschrift Nature Structural & Molecular Biology
Quellenangaben Band: 30, Heft: 12, Seiten: 1913-1924 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
Förderungen Max Planck Society
Swiss National Science Foundation
DFG
European Research Council