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Titin Z1Z2-Telethonin Complex

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Muscle fibers, through their so-called thick and thin filaments, contract and extend in doing their work. To render the fibers elastic and protect them from overstretching, the thick filaments are connected through a long and thin elastic protein, titin, to the base of the fibers. Titin, by far the longest protein in human cells, is a molecular bungee cord and, like such cord, must be affixed firmly to the base. How this is done was a mystery until crystallographers took the first atomic resolution image of the system: it turns out that two titins are spliced together at their ends like ropes. The splicing involves a third small protein, the titin-telethonin-titin system forming a U. The U apparently is thrown over a bollard-like cellular structure to hold the thick filaments much like boats are held by bollards and ropes at their mooring place. The crystallographers teamed up with computational biologists to investigate the mechanical strength of the titin - telethonin - titin cord by means of molecular dynamics simulations using NAMD. As reported recently, the cord has great mechanical strength due to an extended network of hydrogen bonds between beta-strands, common structural features in proteins, that in the present case form a sheet extending through all three proteins. This discovery explains how living cells can splice cellular proteins together through a system of hydrogen-bonded beta-strands that extend through several proteins. Interestingly, such beta-strands were seen previously in cases of diseases like Alzheimers where the feature leads, however, to pathological assembly of proteins. What needs to be understood now is how the telethonin glue is applied only to the right spots in the cell and how the cells prevent telethonin from splicing together the wrong proteins. For more information visit our titin-telethonin web page.