6R9T

Cryo-EM structure of autoinhibited human talin-1

Summary for 6R9T

• Entry DOI: 10.2210/pdb6r9t/pdb
• EMDB information: 4772
• Descriptor: Talin-1 (1 entity in total)
• Functional Keywords: focal adhesion, signaling, actin, vinculin, cell adhesion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 270773.72

Authors

Dedden, D.,Schumacher, S.,Zacharias, M.,Biertumpfel, C.,Mizuno, N. (deposition date: 2019-04-04, release date: 2019-10-16, Last modification date: 2024-05-22)

Primary citation

Dedden, D.,Schumacher, S.,Kelley, C.F.,Zacharias, M.,Biertumpfel, C.,Fassler, R.,Mizuno, N.
The Architecture of Talin1 Reveals an Autoinhibition Mechanism.
Cell, 179:120-131.e13, 2019

PubMed Abstract: 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 PIP 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.

PubMed: 31539492
DOI: 10.1016/j.cell.2019.08.034

Experimental method

ELECTRON MICROSCOPY (6.2 Å)