The Interaction of Vinculin with Actin

Journal Article · Thu Apr 25 00:00:00 EDT 2013 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.1002995· OSTI ID:1627228

Golji, Javad ^[1]; Mofrad, Mohammad R. K. ^[2]

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1. Univ. of California, Berkeley, CA (United States). Depts. of Bioengineering and Mechanical Engineering. Molecular Cell Biomechanics Lab.; DOE/OSTI
2. Univ. of California, Berkeley, CA (United States). Depts. of Bioengineering and Mechanical Engineering. Molecular Cell Biomechanics Lab.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division

Vinculin can interact with F-actin both in recruitment of actin filaments to the growing focal adhesions and also in capping of actin filaments to regulate actin dynamics. Using molecular dynamics, both interactions are simulated using different vinculin conformations. Vinculin is simulated either with only its vinculin tail domain (Vt), with all residues in its closed conformation, with all residues in an open I conformation, and with all residues in an open II conformation. The open I conformation results from movement of domain 1 away from Vt; the open II conformation results from complete dissociation of Vt from the vinculin head domains. Simulation of vinculin binding along the actin filament showed that Vt alone can bind along the actin filaments, that vinculin in its closed conformation cannot bind along the actin filaments, and that vinculin in its open I conformation can bind along the actin filaments. The simulations confirm that movement of domain 1 away from Vt in formation of vinculin 1 is sufficient for allowing Vt to bind along the actin filament. Simulation of Vt capping actin filaments probe six possible bound structures and suggest that vinculin would cap actin filaments by interacting with both S1 and S3 of the barbed-end, using the surface of Vt normally occluded by D4 and nearby vinculin head domain residues. Simulation of D4 separation from Vt after D1 separation formed the open II conformation. Binding of open II vinculin to the barbed-end suggests this conformation allows for vinculin capping. Three binding sites on F-actin are suggested as regions that could link to vinculin. Vinculin is suggested to function as a variable switch at the focal adhesions. The conformation of vinculin and the precise F-actin binding conformation is dependent on the level of mechanical load on the focal adhesion.

• Research Organization: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
• Sponsoring Organization: National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 1627228
• Journal Information: PLoS Computational Biology (Online), Journal Name: PLoS Computational Biology (Online) Journal Issue: 4 Vol. 9; ISSN 1553-7358
• Publisher: Public Library of Science
• Country of Publication: United States
• Language: English

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