Header

UZH-Logo

Maintenance Infos

Conformational states during vinculin unlocking differentially regulate focal adhesion properties


Chorev, Dror S; Volberg, Tova; Livne, Ariel; Eisenstein, Miriam; Martins, Bruno; Kam, Zvi; Jockusch, Brigitte M; Medalia, Ohad; Sharon, Michal; Geiger, Benny (2018). Conformational states during vinculin unlocking differentially regulate focal adhesion properties. Scientific Reports, 8(1):2693.

Abstract

Focal adhesions (FAs) are multi-protein complexes that connect the actin cytoskeleton to the extracellular matrix, via integrin receptors. The growth, stability and adhesive functionality of these structures are tightly regulated by mechanical stress, yet, despite the extensive characterization of the integrin adhesome, the detailed molecular mechanisms underlying FA mechanosensitivity are still unclear. Besides talin, another key candidate for regulating FA-associated mechanosensing, is vinculin, a prominent FA component, which possesses either closed ("auto-inhibited") or open ("active") conformation. A direct experimental demonstration, however, of the conformational transition between the two states is still absent. In this study, we combined multiple structural and biological approaches to probe the transition from the auto-inhibited to the active conformation, and determine its effects on FA structure and dynamics. We further show that the transition from a closed to an open conformation requires two sequential steps that can differentially regulate FA growth and stability.

Abstract

Focal adhesions (FAs) are multi-protein complexes that connect the actin cytoskeleton to the extracellular matrix, via integrin receptors. The growth, stability and adhesive functionality of these structures are tightly regulated by mechanical stress, yet, despite the extensive characterization of the integrin adhesome, the detailed molecular mechanisms underlying FA mechanosensitivity are still unclear. Besides talin, another key candidate for regulating FA-associated mechanosensing, is vinculin, a prominent FA component, which possesses either closed ("auto-inhibited") or open ("active") conformation. A direct experimental demonstration, however, of the conformational transition between the two states is still absent. In this study, we combined multiple structural and biological approaches to probe the transition from the auto-inhibited to the active conformation, and determine its effects on FA structure and dynamics. We further show that the transition from a closed to an open conformation requires two sequential steps that can differentially regulate FA growth and stability.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

6 downloads since deposited on 08 Mar 2018
6 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:9 February 2018
Deposited On:08 Mar 2018 18:57
Last Modified:01 Apr 2018 01:22
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41598-018-21006-8
PubMed ID:29426917

Download

Download PDF  'Conformational states during vinculin unlocking differentially regulate focal adhesion properties'.
Preview
Content: Published Version
Filetype: PDF
Size: 5MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)
Download PDF  'Conformational states during vinculin unlocking differentially regulate focal adhesion properties'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 1MB