THE LIM DOUBLE ZINC-FINGER MOTIF FUNCTIONS AS A PROTEIN DIMERIZATION DOMAIN/

Protein-protein interactions resulting in dimerization and heterodimer ization are of central importance in the control of gene expression an d cell function. Proteins that share the 52-residue LIM/double zinc-fi nger domain are involved in a wide range of developmental and cellular controls. Some of these functions have been hypothesized to involve p rotein dimerization. In the present report we demonstrate, using both in vitro and cell-based studies, that a representative LIM protein, hu man cysteine-rich protein (hCRP), can efficiently homodimerize. The di merization ability of hCRP is mapped to the LIM domains, can be transf erred to an unrelated protein by fusion of a single minimal LIM/double zinc-finger segment, occurs in the absence as well as the presence of DNA, and appears to depend on coordination of two zinc atoms in the f inger doublet. These observations support a specific role for protein dimerization in the function of proteins containing the LIM/double zin c-finger domain and expand the general spectrum of potential interacti ons mediated by zinc-finger motifs.