Calcium binding to glutamate-rich motifs in the PEVK segment of titin reduces its bending rigidity and increases titin-based tension in muscle fibers.
The PEVK segment of titin contains E-rich motifs that bind calcium, altering its conformation and increasing titin-based tension, functioning as a calcium-dependent molecular spring.
Titin (also known as connectin) is a giant protein with a wide range of cellular functions, including providing muscle cells with elasticity. Its physiological extension is largely derived from the PEVK segment, rich in proline (P), glutamate (E), valine (V), and lysine (K) residues. We studied recombinant PEVK molecules containing the two conserved elements: approximately 28-residue PEVK repeats and E-rich motifs. Single molecule experiments revealed that calcium-induced conformational changes reduce the bending rigidity of the PEVK fragments, and site-directed mutagenesis identified four glutamate residues in the E-rich motif that was studied (exon 129), as critical for this process. Experiments with muscle fibers showed that titin-based tension is calcium responsive. We propose that the PEVK segment contains E-rich motifs that render titin a calcium-dependent molecular spring that adapts to the physiological state of the cell.
Labeit et al. (2003) studied this question. Calcium vs. Low calcium (pCa 9) was evaluated on Persistence length (PL) of PEVK fragments and titin-based tension. Calcium binding to glutamate-rich motifs in the PEVK segment of titin reduces its bending rigidity and increases titin-based tension in muscle fibers.