The Architecture of Talin1 Reveals an Autoinhibition Mechanism

Cell. 2019 Sep 19;179(1):120-131.e13. doi: 10.1016/j.cell.2019.08.034.


Focal adhesions (FAs) are protein machineries essential for cell adhesion, migration, and differentiation. Talin is an integrin-activating and tension-sensing FA component directly connecting integrins in the plasma membrane with the actomyosin cytoskeleton. To understand how talin function is regulated, we determined a cryoelectron microscopy (cryo-EM) structure of full-length talin1 revealing a two-way mode of autoinhibition. The actin-binding rod domains fold into a 15-nm globular arrangement that is interlocked by the integrin-binding FERM head. In turn, the rod domains R9 and R12 shield access of the FERM domain to integrin and the phospholipid PIP2 at the membrane. This mechanism likely ensures synchronous inhibition of integrin, membrane, and cytoskeleton binding. We also demonstrate that compacted talin1 reversibly unfolds to an ∼60-nm string-like conformation, revealing interaction sites for vinculin and actin. Our data explain how fast switching between active and inactive conformations of talin could regulate FA turnover, a process critical for cell adhesion and signaling.

Keywords: PIP(2); actin; cryo-EM; cytoskeleton; focal adhesion; mechanosensor; signaling; structure; talin; vinculin.

MeSH terms

  • Actins / metabolism
  • Actomyosin / metabolism
  • Binding Sites
  • Cell Adhesion / physiology
  • Cryoelectron Microscopy
  • Cytoskeleton / metabolism
  • Dimerization
  • Escherichia coli / metabolism
  • Focal Adhesions / metabolism*
  • Humans
  • Integrins / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Interaction Domains and Motifs*
  • Signal Transduction / physiology
  • Talin / chemistry*
  • Talin / metabolism*
  • Vinculin / metabolism


  • Actins
  • Integrins
  • TLN1 protein, human
  • Talin
  • Vinculin
  • Actomyosin