How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism
Upon cell adhesion, talin physically couples the cytoskeleton via integrins to the extracellular matrix, and subsequent vinculin recruitment is enhanced by locally applied tensile force. Since the vinculin binding (VB) sites are buried in the talin rod under equilibrium conditions, the structural me...
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| Format: | Online |
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Public Library of Science
2008
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242828/ |
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pubmed-22428282008-02-15 How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism Hytönen, Vesa P Vogel, Viola Research Article Upon cell adhesion, talin physically couples the cytoskeleton via integrins to the extracellular matrix, and subsequent vinculin recruitment is enhanced by locally applied tensile force. Since the vinculin binding (VB) sites are buried in the talin rod under equilibrium conditions, the structural mechanism of how vinculin binding to talin is force-activated remains unknown. Taken together with experimental data, a biphasic vinculin binding model, as derived from steered molecular dynamics, provides high resolution structural insights how tensile mechanical force applied to the talin rod fragment (residues 486–889 constituting helices H1–H12) might activate the VB sites. Fragmentation of the rod into three helix subbundles is prerequisite to the sequential exposure of VB helices to water. Finally, unfolding of a VB helix into a completely stretched polypeptide might inhibit further binding of vinculin. The first events in fracturing the H1–H12 rods of talin1 and talin2 in subbundles are similar. The proposed force-activated α-helix swapping mechanism by which vinculin binding sites in talin rods are exposed works distinctly different from that of other force-activated bonds, including catch bonds. Public Library of Science 2008-02 2008-02-15 /pmc/articles/PMC2242828/ /pubmed/18282082 http://dx.doi.org/10.1371/journal.pcbi.0040024 Text en © 2008 Hytönen and Vogel. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Hytönen, Vesa P Vogel, Viola |
| spellingShingle |
Hytönen, Vesa P Vogel, Viola How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism |
| author_facet |
Hytönen, Vesa P Vogel, Viola |
| author_sort |
Hytönen, Vesa P |
| title |
How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism |
| title_short |
How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism |
| title_full |
How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism |
| title_fullStr |
How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism |
| title_full_unstemmed |
How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism |
| title_sort |
how force might activate talin's vinculin binding sites: smd reveals a structural mechanism |
| description |
Upon cell adhesion, talin physically couples the cytoskeleton via integrins to the extracellular matrix, and subsequent vinculin recruitment is enhanced by locally applied tensile force. Since the vinculin binding (VB) sites are buried in the talin rod under equilibrium conditions, the structural mechanism of how vinculin binding to talin is force-activated remains unknown. Taken together with experimental data, a biphasic vinculin binding model, as derived from steered molecular dynamics, provides high resolution structural insights how tensile mechanical force applied to the talin rod fragment (residues 486–889 constituting helices H1–H12) might activate the VB sites. Fragmentation of the rod into three helix subbundles is prerequisite to the sequential exposure of VB helices to water. Finally, unfolding of a VB helix into a completely stretched polypeptide might inhibit further binding of vinculin. The first events in fracturing the H1–H12 rods of talin1 and talin2 in subbundles are similar. The proposed force-activated α-helix swapping mechanism by which vinculin binding sites in talin rods are exposed works distinctly different from that of other force-activated bonds, including catch bonds. |
| publisher |
Public Library of Science |
| publishDate |
2008 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242828/ |
| _version_ |
1611439024239542272 |