Molecular basis of the mechanical hierarchy in myomesin dimers for sarcomere integrity.

ABSTRACT: Myomesin is one of the most important structural molecules constructing the M-band in the force-generating unit of striated muscle, and a critical structural maintainer of the sarcomere. Using molecular dynamics simulations, we here dissect the mechanical properties of the structurally known building blocks of myomesin, namely ?-helices, immunoglobulin (Ig) domains, and the dimer interface at myomesin's 13th Ig domain, covering the mechanically important C-terminal part of the molecule. We find the interdomain ?-helices to be stabilized by the hydrophobic interface formed between the N-terminal half of these helices and adjacent Ig domains, and, interestingly, to show a rapid unfolding and refolding equilibrium especially under low axial forces up to ? 15 pN. These results support and yield atomic details for the notion of recent atomic-force microscopy experiments, namely, that the unique helices inserted between Ig domains in myomesin function as elastomers and force buffers. Our results also explain how the C-terminal dimer of two myomesin molecules is mechanically outperforming the helices and Ig domains in myomesin and elsewhere, explaining former experimental findings. This study provides a fresh view onto how myomesin integrates elastic helices, rigid immunoglobulin domains, and an extraordinarily resistant dimer into a molecular structure, to feature a mechanical hierarchy that represents a firm and yet extensible molecular anchor to guard the stability of the sarcomere.

SUBMITTER: Xiao S 

PROVIDER: S-EPMC4142248 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature