TCB Publications - Abstract

Eric H. Lee, Mu Gao, Nikos Pinotsis, Matthias Wilmanns, and Klaus Schulten. Mechanical strength of the titin Z1Z2/telethonin complex. Structure, 14:497-509, 2006.

LEE2006 Using molecular dynamics simulations, we have explored the mechanical strength of the titin Z1Z2-telethonin complex, namely, its ability to bear strong forces such as those encountered during passive muscle stretch. Our results show that not only does this complex resist high levels of mechanical force, suggesting that telethonin is a major component of the N-terminal titin anchor, but also that telethonin acts to distribute these forces between its two joined titin Z2 domains to protect the proximal Z1 domain from bearing too much stress. Our simulations also reveal that without telethonin, apo-titin Z1Z2 exhibits significantly decreased resistance to mechanical stress, and that the N-terminal segment of telethonin (residues 1-89) does not exhibit a stable fold conformation when it is unbound from titin Z1Z2. Consequently, our study sheds light on a key but little studied architectural feature of biological cells, the existence of strong mechanical links that glue separate proteins together.

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