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

Mingxi Yao, Benjamin T. Goult, Hu Chen, Peiwen Cong, Michael Sheetz, Jie Yan

Research output: Contribution to journalArticle

128 Citations (Scopus)

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 a ̂1/45a €...pN, suggesting that 5a €...pN is the force threshold for vinculin binding and adhesion progression.

Original languageEnglish (US)
Article number4610
JournalScientific reports
Volume4
DOIs
StatePublished - Apr 9 2014
Externally publishedYes

Fingerprint

Talin
Vinculin
Focal Adhesions
Mutation
Growth

ASJC Scopus subject areas

  • General

Cite this

Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation. / Yao, Mingxi; Goult, Benjamin T.; Chen, Hu; Cong, Peiwen; Sheetz, Michael; Yan, Jie.

In: Scientific reports, Vol. 4, 4610, 09.04.2014.

Research output: Contribution to journalArticle

Yao, Mingxi ; Goult, Benjamin T. ; Chen, Hu ; Cong, Peiwen ; Sheetz, Michael ; Yan, Jie. / Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation. In: Scientific reports. 2014 ; Vol. 4.
@article{6f15d58428164aadb5fe3b25b4200ec0,
title = "Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation",
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 a ̂1/45a €...pN, suggesting that 5a €...pN is the force threshold for vinculin binding and adhesion progression.",
author = "Mingxi Yao and Goult, {Benjamin T.} and Hu Chen and Peiwen Cong and Michael Sheetz and Jie Yan",
year = "2014",
month = "4",
day = "9",
doi = "10.1038/srep04610",
language = "English (US)",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

AU - Yao, Mingxi

AU - Goult, Benjamin T.

AU - Chen, Hu

AU - Cong, Peiwen

AU - Sheetz, Michael

AU - Yan, Jie

PY - 2014/4/9

Y1 - 2014/4/9

N2 - 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 a ̂1/45a €...pN, suggesting that 5a €...pN is the force threshold for vinculin binding and adhesion progression.

AB - 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 a ̂1/45a €...pN, suggesting that 5a €...pN is the force threshold for vinculin binding and adhesion progression.

UR - http://www.scopus.com/inward/record.url?scp=84898467976&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898467976&partnerID=8YFLogxK

U2 - 10.1038/srep04610

DO - 10.1038/srep04610

M3 - Article

VL - 4

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 4610

ER -