The F1 loop of the talin head domain acts as a gatekeeper in integrin activation and clustering

Show full item record



Kukkurainen , S , Azizi , L , Zhang , P , Jacquier , M-C , Baikoghli , M , von Essen , M , Tuukkanen , A , Laitaoja , M , Liu , X , Rahikainen , R , Orlowski , A , Jänis , J , Määttä , J A E , Varjosalo , M , Vattulainen , I , Rog , T , Svergun , D , Cheng , R H , Wu , J , Hytönen , V P & Wehrle-Haller , B 2020 , ' The F1 loop of the talin head domain acts as a gatekeeper in integrin activation and clustering ' , Journal of Cell Science , vol. 133 , no. 19 , 239202 .

Title: The F1 loop of the talin head domain acts as a gatekeeper in integrin activation and clustering
Author: Kukkurainen, Sampo; Azizi, Latifeh; Zhang, Pingfeng; Jacquier, Marie-Claude; Baikoghli, Mo; von Essen, Magdalena; Tuukkanen, Anne; Laitaoja, Mikko; Liu, Xiaonan; Rahikainen, Rolle; Orlowski, Adam; Jänis, Janne; Määttä, Juha A. E.; Varjosalo, Markku; Vattulainen, Ilpo; Rog, Tomasz; Svergun, Dmitri; Cheng, R. Holland; Wu, Jinhua; Hytönen, Vesa P.; Wehrle-Haller, Bernhard
Contributor organization: Institute of Biotechnology
Molecular Systems Biology
Department of Physics
Date: 2020-10
Language: eng
Number of pages: 15
Belongs to series: Journal of Cell Science
ISSN: 0021-9533
Abstract: Integrin activation and clustering by talin are early steps of cell adhesion. Membrane-bound talin head domain and kindlin bind to the beta integrin cytoplasmic tail, cooperating to activate the heterodimeric integrin, and the talin head domain induces integrin clustering in the presence of Mn2+. Here we show that kindlin-1 can replace Mn2+ to mediate beta 3 integrin clustering induced by the talin head, but not that induced by the F2-F3 fragment of talin. Integrin clustering mediated by kindlin-1 and the talin head was lost upon deletion of the flexible loop within the talin head F1 subdomain. Further mutagenesis identified hydrophobic and acidic motifs in the F1 loop responsible for beta 3 integrin clustering. Modeling, computational and cysteine crosslinking studies showed direct and catalytic interactions of the acidic F1 loop motif with the juxtamembrane domains of alpha- and beta 3-integrins, in order to activate the beta 3 integrin heterodimer, further detailing the mechanism by which the talin-kindlin complex activates and clusters integrins. Moreover, the F1 loop interaction with the beta 3 integrin tail required the newly identified compact FERM fold of the talin head, which positions the F1 loop next to the inner membrane clasp of the talin-bound integrin heterodimer. This article has an associated First Person interview with the first author of the paper.
Subject: Activation
Cell adhesion
Molecular dynamics
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
jcs239202.full.pdf 8.779Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record