Calcium-dependent molecular spring elements in the giant protein titin

Dietmar Labeit, Kaori Watanabe, Christian Witt, Hideaki Fujita, Yiming Wu, Sunshine Lahmers, Theodor Funck, Siegfried Labeit, Henk Granzier

Research output: Contribution to journalArticlepeer-review

321 Scopus citations


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: ≈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.

Original languageEnglish (US)
Pages (from-to)13716-13721
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Nov 11 2003

ASJC Scopus subject areas

  • General


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