Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem

J Cell Biol. 2019 Jun 3;218(6):1799-1809. doi: 10.1083/jcb.201810061. Epub 2019 Apr 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Humans
  • Integrins / metabolism*
  • Lipids / physiology*
  • Mutation
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Shelterin Complex
  • Talin / chemistry
  • Talin / genetics
  • Talin / metabolism*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism*


  • Integrins
  • Lipids
  • Shelterin Complex
  • TERF2IP protein, human
  • TLN1 protein, human
  • Talin
  • Telomere-Binding Proteins