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

The cytoskeletal protein alpha -catenin, which shares structural similarity with vinculin, is required for cadherin-mediated cell adhesion, and functi ons to modulate cell adhesive strength and to link the cadherins to the act in-based cytoskeleton. Here we describe the crystal structure of a region o f alpha -catenin (residues 377-633) termed the M-fragment. The M-fragment i s composed of a tandem repeat of two antiparallel four-helix bundles of vir tually identical architectures that are related in structure to the dimeriz ation domain of (alpha -catenin and the tail region of vinculin. These resu lts suggest that (alpha -catenin is composed of repeating antiparallel heli cal domains. The region of (alpha -catenin previously defined as an adhesio n modulation domain corresponds to the C-terminal four-helix bundle of the M-fragment, and in the crystal lattice these domains exist as dimers. Evide nce for dimerization of the M-fragment of alpha -catenin in solution was de tected by chemical crosslinking experiments. The tendency of the adhesion m odulation domain to form dimers may explain its biological activity of prom oting cell-cell adhesiveness by inducing lateral dimerization of the associ ated cadherin molecule.