Date of Award

2007

Degree Type

Thesis

Degree Name

Master of Science

Program

Biochemistry

Supervisor

Dr. Eric Ball

Abstract

The C-terminal domain of vinculin, a protein of adherens junctions, is thought to undergo conformational changes upon binding actin or acidic phospholipid. For the present study, cysteine residues were inserted to form disulfide bonds to prevent motion in the arm (residues 1048-1066), strap (residues 878-896) or both regions. The ability of these mutant domains to interact with the head domain was unaffected in a fluorescence binding assay. In cosedimentation assays under oxidizing conditions, the mutants showed decreased binding to actin and acidic phospholipid. The low-shear falling ball assay of viscosity provided evidence that all three mutants have a decreased capacity for crosslinking actin filaments under oxidizing conditions. Thus, local conformational changes, notably in the strap and arm regions in the tail appear to assist interaction with these ligands. This agrees with a current model for actin interactions; however, data from this study supports a revised model for lipid binding in that the arm ‘stretches out’ so that basic residues in it can bind to the lipid bilayer at the same time as basic residues within the tail bundle itself

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