Crystal structure of the M-fragment of alpha-catenin: implications for modulation of cell adhesion

Open Access
Publisher Website
Google Scholar
Abstract
The cytoskeletal protein α‐catenin, which shares structural similarity with vinculin, is required for cadherin‐mediated cell adhesion, and functions to modulate cell adhesive strength and to link the cadherins to the actin‐based cytoskeleton. Here we describe the crystal structure of a region of α‐catenin (residues 377–633) termed the M‐fragment. The M‐fragment is composed of a tandem repeat of two antiparallel four‐helix bundles of virtually identical architectures that are related in structure to the dimerization domain of α‐catenin and the tail region of vinculin. These results suggest that α‐catenin is composed of repeating antiparallel helical domains. The region of α‐catenin previously defined as an adhesion modulation domain corresponds to the C‐terminal four‐helix bundle of the M‐fragment, and in the crystal lattice these domains exist as dimers. Evidence for dimerization of the M‐fragment of α‐catenin in solution was detected by chemical cross‐linking experiments. The tendency of the adhesion modulation domain to form dimers may explain its biological activity of promoting cell–cell adhesiveness by inducing lateral dimerization of the associated cadherin molecule.