Format

Send to

Choose Destination
Sci Rep. 2014 Apr 9;4:4610. doi: 10.1038/srep04610.

Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation.

Author information

1
1] Mechanobiology Institute, National University of Singapore, 117411, Singapore [2].
2
1] Department of Biochemistry, University of Leicester, Henry Wellcome Building, Leicester, LE1 9HN, UK [2].
3
1] Mechanobiology Institute, National University of Singapore, 117411, Singapore [2] Department of Physics, Xiamen University, Xiamen, Fujian, 361005, China.
4
1] Mechanobiology Institute, National University of Singapore, 117411, Singapore [2] Singapore-MIT Alliance for Research and Technology, National University of Singapore, 117543, Singapore.
5
1] Mechanobiology Institute, National University of Singapore, 117411, Singapore [2] Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
6
1] Mechanobiology Institute, National University of Singapore, 117411, Singapore [2] Department of Physics, National University of Singapore, 117542, Singapore [3] Centre for Bioimaging Sciences, National University of Singapore, 117546, Singapore.

Abstract

The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at ∼5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression.

PMID:
24714394
PMCID:
PMC3980218
DOI:
10.1038/srep04610
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center