Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
03 06 2019
03 06 2019
Historique:
received:
12
10
2018
revised:
11
02
2019
accepted:
28
03
2019
pubmed:
17
4
2019
medline:
10
4
2020
entrez:
17
4
2019
Statut:
ppublish
Résumé
Rap1 GTPases bind effectors, such as RIAM, to enable talin1 to induce integrin activation. In addition, Rap1 binds directly to the talin1 F0 domain (F0); however, this interaction makes a limited contribution to integrin activation in CHO cells or platelets. Here, we show that talin1 F1 domain (F1) contains a previously undetected Rap1-binding site of similar affinity to that in F0. A structure-guided point mutant (R118E) in F1, which blocks Rap1 binding, abolishes the capacity of Rap1 to potentiate talin1-induced integrin activation. The capacity of F1 to mediate Rap1-dependent integrin activation depends on a unique loop in F1 that has a propensity to form a helix upon binding to membrane lipids. Basic membrane-facing residues of this helix are critical, as charge-reversal mutations led to dramatic suppression of talin1-dependent activation. Thus, a novel Rap1-binding site and a transient lipid-dependent helix in F1 work in tandem to enable a direct Rap1-talin1 interaction to cause integrin activation.
Identifiants
pubmed: 30988001
pii: jcb.201810061
doi: 10.1083/jcb.201810061
pmc: PMC6548133
doi:
Substances chimiques
Integrins
0
Lipids
0
Shelterin Complex
0
TERF2IP protein, human
0
TLN1 protein, human
0
Talin
0
Telomere-Binding Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1799-1809Subventions
Organisme : NHLBI NIH HHS
ID : K01 HL133530
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL078784
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL139947
Pays : United States
Organisme : NIH HHS
ID : S10 OD021831
Pays : United States
Informations de copyright
© 2019 Gingras et al.
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