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

Sampo Kukkurainen, Latifeh Azizi, Pingfeng Zhang, Marie Claude Jacquier, Mo Baikoghli, Magdaléna von Essen, Anne Tuukkanen, Mikko Laitaoja, Xiaonan Liu, Rolle Rahikainen, Adam Orłowski, Janne Jänis, Juha A. E. Määttä, Markku Varjosalo, Ilpo Vattulainen, Tomasz Róg, Dmitri Svergun, R. Holland Cheng, Jinhua Wu, Vesa P. HytönenBernhard Wehrle-Haller

Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

4 Sitaatiot (Scopus)
13 Lataukset (Pure)

Abstrakti

Integrin activation and clustering by talin are early steps of cell adhesion. Membrane-bound talin head domain and kindlin bind to the β 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 β3 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 β3 integrin clustering. Modeling, computational and cysteine crosslinking studies showed direct and catalytic interactions of the acidic F1 loop motif with the juxtamembrane domains of α- and β3-integrins, in order to activate the β3 integrin heterodimer, further detailing the mechanism by which the talin-kindlin complex activates and clusters integrins. Moreover, the F1 loop interaction with the β3 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.

AlkuperäiskieliEnglanti
JulkaisuJournal of cell science
Vuosikerta133
Numero19
DOI - pysyväislinkit
TilaJulkaistu - 12 lokak. 2020
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

  • Jufo-taso 2

!!ASJC Scopus subject areas

  • Cell Biology

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