title: Fast-folding alpha-helices as reversible strain absorbers in the muscle protein myomesin.
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.
authors.affiliation: Physik Department E22, Technische Universität München, James-Franck-Straße, 85748 Garching, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Berkemeier
authors.forename: Morten
authors.initials: M
authors.lastname: Bertz
authors.forename: Senbo
authors.initials: S
authors.lastname: Xiao
authors.forename: Nikos
authors.initials: N
authors.lastname: Pinotsis
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
authors.forename: Frauke
authors.initials: F
authors.lastname: Gräter
authors.forename: Matthias
authors.initials: M
authors.lastname: Rief
mesh_terms: D001696:Biomechanical Phenomena; D064211:Connectin; D007700:Kinetics; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D009124:Muscle Proteins / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding
chemical_list: D064211:Connectin; D009124:Muscle Proteins