Molecular dissection of a LIM domain.

Abstract

LIM domains are novel sequence elements that are found in more than 60 gene products, many of which function as key regulators of developmental pathways. The LIM domain, characterized by the cysteine-rich consensus CX2CX16-23HX2CX2CX2CX16-21 CX2-3(C/H/ D), is a specific mental-binding structure that consists of two distinct zinc-binding subdomains. We and others have recently demonstrated that the LIM domain mediates protein-protein interactions. However, the sequences that define the protein-binding specificity of the LIM domain had not yet been identified. Because structural studies have revealed that the C-terminal zinc-binding module of a LIM domain displays a tertiary fold compatible with nucleic acid binding, it was of interest to determine whether the specific protein-binding activity of a LIM domain could be ascribed to one of its two zinc-binding subdomains. To address this question, we have analyzed the protein-binding capacity of a model LIM peptide, called zLIM1, that is derived from the cytoskeletal protein zyxin. These studies demonstrate that the protein-binding function of zLIM1 can be mapped to sequences contained within its N-terminal zinc-binding module. The C-terminal zinc-binding module of zLIM1 may thus remain accessible to additional interactive partners. Our results raise the possibility that the two structural subdomains of a LIM domain are capable of performing distinct biochemical functions.

Ajuba, a Novel LIM Protein, Interacts with Grb2, Augments Mitogen-Activated Protein Kinase Activity in Fibroblasts, and Promotes Meiotic Maturation of Xenopus Oocytes in a Grb2- and Ras-Dependent Manner

“…They are thought to function as versatile protein modules, capable of acting within diverse cellular contexts and in multiple subcellular compartments. Many have been shown to participate in direct protein-protein interactions, and they may also have the capacity to bind DNA directly (5,17,34). Structural analysis of LIM domains suggest that most adopt a similar zinc-bound finger; however, no protein has been identified as a common target for LIM domains (28).…”

The plant LIM proteins: unlocking the hidden attractions

“…The animal LIMs are one of the widely studied LIM proteins known in eukaryotes and provide function related to development and disease (Hobert and Westphal 2000;Kadrmas and Beckerle 2004;Matthews et al 2013). The known LIM domain in the plant always has either H (in 2LIMs) or C (in DA1/DAR) as last amino acid residue and not D (aspartate) which is reported in some animal CRPs (Schmeichel and Beckerle 1997). Moreover, the plant LIM proteins also have comparatively longer C-terminal and are short of glycine-rich region (GRR) following each LIM domain (Arnaud et al 2007).…”

“…The individual LIM domain was recognized as a protein-protein interaction module which represents a consensus sequence as [C-X 2 -C-X 16-23 -H-X 2 -C]-X 2 -[C-X 2 -C-X 16-21 C-X 2-3 -(C/D/H)] (Kadrmas and Beckerle 2004). The universal make-up of LIM domain comprises two zinc fingers linked together with a short two-amino acid spacer (Sadler et al 1992;Pérez-Alvarado et al 1994;Schmeichel and Beckerle 1997;Yao et al 1999). This protein family has been addressed for features related to animal system mostly covering the aspects of cytoskeletal organization, development and diseases (Zheng and Zhao 2007).…”

Actin bundling in plants

“…The LIM domain is a tandem zinc finger motif of (55 amino acids that basically function in protein-protein interactions) [Schmeichel and Beckerle, 1997;Kadrmas and Beckerle, 2004]. Whereas animals possess numerous LIM proteins of diverse structures and functions, plants only contain a limited number of LIM proteins [Arnaud et al, 2007].…”