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

Felix Berkemeier, Morten Bertz, Senbo Xiao, Nikos Pinotsis, Matthias Wilmanns, Frauke Gräter, Matthias Rief

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 α-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 α-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 α-helix unfolding mechanically protects the molecule homodimerization from dissociation at physiologically relevant forces. As fast and reversible molecular springs the myomesin α-helical linkers are an essential component for the structural integrity of the M band.

Original languageEnglish
Pages (from-to)14139-14144
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number34
DOIs
Publication statusPublished - 2011 Aug 23

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Connectin
Muscle Proteins
Myeloma Proteins
Sarcomeres
Molecular Dynamics Simulation
Mechanics
Muscles
Proteins
Immunoglobulin Domains

Keywords

  • Atomic force microscopy
  • Protein folding

ASJC Scopus subject areas

  • General

Cite this

Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin. / Berkemeier, Felix; Bertz, Morten; Xiao, Senbo; Pinotsis, Nikos; Wilmanns, Matthias; Gräter, Frauke; Rief, Matthias.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 34, 23.08.2011, p. 14139-14144.

Research output: Contribution to journalArticle

Berkemeier, Felix ; Bertz, Morten ; Xiao, Senbo ; Pinotsis, Nikos ; Wilmanns, Matthias ; Gräter, Frauke ; Rief, Matthias. / Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 34. pp. 14139-14144.
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