Vinculin tail conformation and self-association is independent of pH and H906 protonation.


Journal Article

Vinculin is a highly conserved cytoskeletal protein that localizes to sites of cell adhesion. The tail domain of vinculin (Vt) forms tight autoinhibitory interactions with the head domain and down-regulates vinculin function by obscuring ligand binding sites. Ligand binding is required for both vinculin activation and function, and one of vinculin's primary roles as a cell adhesion protein involves its ability to link the Actin cytoskeleton to the cell membrane. Vt can bind F-Actin and phosphoinositol 4,5-bisphosphate, and association with these ligands has been reported to cause a conformational change in Vt. Moreover, a single histidine residue, H906, was reported to be critical for both a pH dependent conformational change and pH dependent self-association. In this study, we investigate the role of pH on Vt structure and self-association. In contrast to earlier observations, our studies do not support a significant alteration in Vt conformation over this pH range. Moreover, while we identify a site of Vt dimerization, similar to that observed previously by X-ray crystallography, the weak K(d) (approximately 300 microM) determined for Vt self-association does not differ significantly between pH 5.5 and pH 7.5.

Full Text

Duke Authors

Cited Authors

  • Palmer, SM; Schaller, MD; Campbell, SL

Published Date

  • November 25, 2008

Published In

Volume / Issue

  • 47 / 47

Start / End Page

  • 12467 - 12475

PubMed ID

  • 18980387

Pubmed Central ID

  • 18980387

Electronic International Standard Serial Number (EISSN)

  • 1520-4995

Digital Object Identifier (DOI)

  • 10.1021/bi801764a


  • eng

Conference Location

  • United States