SEQUENTIAL ASSIGNMENT OF H-1, N-15, C-13 RESONANCES AND SECONDARY STRUCTURE OF HUMAN CALMODULIN-LIKE PROTEIN DETERMINED BY NMR-SPECTROSCOPY

Human calmodulin-like protein (CLP) is closely related to vertebrate c almodulin, yet its unique cell specific expression pattern, overlappin g but divergent biochemical properties, and specific target proteins s uggest that it is not an isoform of calmodulin. To gain insight into t he structural differences that may underlie the difference target spec ificities and biochemical properties of CLP when compared to calmoduli n, we determined the sequential backbone assignment and associated sec ondary structure of 144 out of the 148 residues of Ca2+-CLP by using m ultinuclear multidimensional NMR spectroscopy. Despite a very high ove rall degree of structural similarity between CLP and calmodulin, a num ber of significant differences were found mainly in the length of alph a-helices and in the central nonhelical flexible region. Interestingly , the regions of greatest primary sequence divergence between CLP and calmodulin in helices III and VIII displayed only minor secondary stru cture differences. The data suggest that the distinct differences in t arget specificity and biochemical properties of CLP and calmodulin res ult from the sum of several minor structural and side-chain changes sp read over multiple domains in these proteins.