RESUMEN
Calsequestrin (CASQ) exists as two distinct isoforms CASQ1 and CASQ2 in all vertebrates. Although the isoforms exhibit unique functional characteristic, the structural basis for the same is yet to be fully defined. Interestingly, the C-terminal region of the two isoforms exhibit significant differences both in length and amino acid composition; forming Dn-motif and DEXn-motif in CASQ1 and CASQ2, respectively. Here, we investigated if the unique C-terminal motifs possess Ca(2+)-sensitivity and affect protein function. Sequence analysis shows that both the Dn- and DEXn-motifs are intrinsically disordered regions (IDRs) of the protein, a feature that is conserved from fish to man. Using purified synthetic peptides, we show that these motifs undergo distinctive Ca(2+)-mediated folding suggesting that these disordered motifs are Ca(2+)-sensitivity. We generated chimeric proteins by swapping the C-terminal portions between CASQ1 and CASQ2. Our studies show that the C-terminal portions do not play significant role in protein folding. An interesting finding of the current study is that the switching of the C-terminal portion completely reverses the polymerization kinetics. Collectively, these data suggest that these Ca(2+)-sensitivity IDRs located at the back-to-back dimer interface influence isoform-specific Ca(2+)-dependent polymerization properties of CASQ.