Fast-folding alpha-helices as reversible strain absorbers in the muscle protein myomesin

Citation:

Berkemeier F, Bertz M, Xiao S, Pinotsis N, Wilmanns M, Grater F, Rief M. Fast-folding alpha-helices as reversible strain absorbers in the muscle protein myomesin. Proc Natl Acad Sci U S A. 2011;108:14139-44.

Abstract:

The highly oriented filamentous protein network of muscle constantly experiences significant mechanical load during muscle operation. The dimeric protein myomesin has been identified as an important M-band component supporting the mechanical integrity of the entire sarcomere. Recent structural studies have revealed a long alpha-helical linker between the C-terminal immunoglobulin (Ig) domains My12 and My13 of myomesin. In this paper, we have used single-molecule force spectroscopy in combination with molecular dynamics simulations to characterize the mechanics of the myomesin dimer comprising immunoglobulin domains My12-My13. We find that at forces of approximately 30 pN the alpha-helical linker reversibly elongates allowing the molecule to extend by more than the folded extension of a full domain. High-resolution measurements directly reveal the equilibrium folding/unfolding kinetics of the individual helix. We show that alpha-helix unfolding mechanically protects the molecule homodimerization from dissociation at physiologically relevant forces. As fast and reversible molecular springs the myomesin alpha-helical linkers are an essential component for the structural integrity of the M band.

Notes:

Berkemeier, FelixBertz, MortenXiao, SenboPinotsis, NikosWilmanns, MatthiasGrater, FraukeRief, MatthiasengResearch Support, Non-U.S. Gov'tProc Natl Acad Sci U S A. 2011 Aug 23;108(34):14139-44. doi: 10.1073/pnas.1105734108. Epub 2011 Aug 8.

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Biochemistry, Chemistry Department
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Associate Professor, Chemistry