Solution structure of the chicken cysteine-rich protein, CRP1, a double-LIM protein implicated in muscle differentiation

The mechanism by which the contractile machinery of muscle is assembled and maintained is not well-understood. Members of the cysteine-rich protein (C RP) family have been implicated in these processes. Three vertebrate CRPs ( CRP1-3) that exhibit developmentally regulated muscle-specific expression h ave been identified. All three proteins are associated with the actin cytos keleton, and one has been shown to be required for striated muscle structur e and function. The vertebrate CRPs identified to date display a similar mo lecular architecture; each protein is comprised of two tandemly arrayed LIM domains, protein-binding motifs found in a number of proteins with roles i n cell differentiation. Each LIM domain coordinates two Zn(II) ions that ar e bound independently in CCHC (C=Cys, H=His) and CCCC modules. Here we desc ribe the solution structure of chicken CRP1 determined by homonuclear and H -1-N-15 heteronuclear magnetic resonance spectroscopy, Comparison of the st ructures of the two LIM domains of CRP1 reveals a high degree of similarity in their tertiary folds. In addition, the two component LIM domains repres ent two completely independent folding units and exhibit no apparent intera ctions with each other. The structural independence and spatial separation of the two LIM domains of CRP1 are compatible with an adapter or linker rol e for the protein.