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The giant protein titin helps build muscles

Imagine grabbing two snakes by the tail so that they can't wriggle off in opposite directions. Scientists at the Hamburg Outstation of the European Molecular Biology Laboratory (EMBL) and collaborators from King's College in London have now discovered that something similar happens to a protein that is crucial in the formation of muscle tissue. Their work appears in the current issue of the journal Nature.

Under the microscope, muscle looks like millions of tiny pistons, stacked end-to-end into long rows. These structures, called sarcomeres, permit the contraction and relaxation of muscle that allow our bodies to move. Sarcomeres are connected at the ends by Z-disks, thick bands of densely-packed molecules. "Sarcomeres are very complex structures, and for many years we've been investigating the steps by which they are formed," says Matthias Wilmanns, Head of the EMBL Hamburg Outstation. "That probably starts when proteins link up to each other in very big assemblies. The meeting point is the Z-disk, but unraveling the connections has been difficult."

Wilmanns' lab and the team of Mathias Gautel, an EMBL alumnus and now at King's College, have thought that a molecule called titin, the largest protein made by human cells, is involved. Titin is anchored in the Z-disk and is so long that it spans half the length of a sarcomere. Its size and position ?putting it into contact with all the majorcomponents of sarcomeres ?suggests that it might help in their assembly.

The latest study, which arises from more than a decade of collaborative research by the Wilmanns and Gautel teams, gives a solution to how this might happen. Peijian Zou and Nikos Pinotsis from the Wilmanns lab obtained crystals of parts of the titin molecule bound to another protein, called telethonin. They analyzed the crystals on high-energy X-ray beamlines at EMBL's Hamburg station, on the site of the German Electron Synchrotron Radiation Facility (DESY). From the extremely d
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Source:European Molecular Biology Laboratory


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