The enigma of LIM domains. Gill G N Structure (London, England : 1993) LIM domains are two-zinc-finger structures found in proteins that have diverse functions. They are proposed to be protein dimerization motifs that assemble protein complexes necessary for growth, development and adaptive responses.

Cysteine-rich LIM domains of LIM-homeodomain and LIM-only proteins contain zinc but not iron. Archer V E,Breton J,Sanchez-Garcia I,Osada H,Forster A,Thomson A J,Rabbitts T H Proceedings of the National Academy of Sciences of the United States of America The structure of LIM domains has major implications for transcription because proteins such as Is1-1 contain two LIM domains associated with a homeodomain, and RBTN1/Ttg-1 and RBTN2/Ttg-2 contain two LIM domains but no homeodomain. Conserved cysteine and histidine residues in the LIM domains suggest a metal-binding role. RBTN and Is1-1 LIM proteins have been made in Escherichia coli and insect cell expression systems and their metal content has been determined using atomic absorption spectroscopy and electron paramagnetic resonance spectroscopy. LIM proteins expressed in soluble form contain zinc atoms, whereas bacterial inclusion bodies invariably also have Fe-S clusters. The latter are identified as linear [Fe3S4]+ clusters and appear to result from incorrect metal coordination by E. coli. These studies show that RBTN1, RBTN2, and Is1-1 are metalloproteins that contain zinc but not iron and, therefore, that the LIM domain represents a zinc-binding domain. 10.1073/pnas.91.1.316

LIM domain proteins. Dawid I B,Toyama R,Taira M Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie The LIM domain is a cysteine-rich domain composed of 2 special zinc fingers that are joined by a 2-amino acid spacer. Some proteins are constituted by LIM domains only while others contain a variety of different functional domains. LIM proteins form a diverse group which includes transcription factors and cytoskeletal proteins. The primary role of LIM domains appears to be in protein-protein interaction, through the formation of dimers with identical or different LIM domains or by binding distinct proteins. In LIM homeodomain proteins, LIM domains seem to function as negative regulatory domains. LIM homeodomain proteins are involved in the control of cell lineage determination and the regulation of differentiation, and LIM-only proteins may have similar roles. LIM-only proteins are also implicated in the control of cell proliferation since several genes encoding such proteins are associated with oncogenic chromosome translocations. In analyzing sequence relationships between LIM domains we suggest that they may be arranged into 5 groups which appear to correlate with the structural and functional properties of the proteins containing these domains.

The LIM/double zinc-finger motif functions as a protein dimerization domain. Feuerstein R,Wang X,Song D,Cooke N E,Liebhaber S A Proceedings of the National Academy of Sciences of the United States of America Protein-protein interactions resulting in dimerization and heterodimerization are of central importance in the control of gene expression and cell function. Proteins that share the 52-residue LIM/double zinc-finger domain are involved in a wide range of developmental and cellular controls. Some of these functions have been hypothesized to involve protein dimerization. In the present report we demonstrate, using both in vitro and cell-based studies, that a representative LIM protein, human cysteine-rich protein (hCRP), can efficiently homodimerize. The dimerization ability of hCRP is mapped to the LIM domains, can be transferred 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 finger doublet. These observations support a specific role for protein dimerization in the function of proteins containing the LIM/double zinc-finger domain and expand the general spectrum of potential interactions mediated by zinc-finger motifs. 10.1073/pnas.91.22.10655