Toward Understanding the Molecular Bases of Stretch Activation: A STRUCTURAL COMPARISON OF THE TWO TROPONIN C ISOFORMS OF LETHOCERUS

J Biol Chem. 2016 Jul 29;291(31):16090-9. doi: 10.1074/jbc.M116.726646. Epub 2016 May 20.

Abstract

Muscles are usually activated by calcium binding to the calcium sensory protein troponin-C, which is one of the three components of the troponin complex. However, in cardiac and insect flight muscle activation is also produced by mechanical stress. Little is known about the molecular bases of this calcium-independent activation. In Lethocerus, a giant water bug often used as a model system because of its large muscle fibers, there are two troponin-C isoforms, called F1 and F2, that have distinct roles in activating the muscle. It has been suggested that this can be explained either by differences in structural features or by differences in the interactions with other proteins. Here we have compared the structural and dynamic properties of the two proteins and shown how they differ. We have also mapped the interactions of the F2 isoform with peptides spanning the sequence of its natural partner, troponin-I. Our data have allowed us to build a model of the troponin complex and may eventually help in understanding the specialized function of the F1 and F2 isoforms and the molecular mechanism of stretch activation.

Keywords: muscle; protein-protein interaction; stress; structural biology; structure-function.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Heteroptera / genetics
  • Heteroptera / metabolism*
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Muscle Fibers, Skeletal / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Troponin C / genetics
  • Troponin C / metabolism*

Substances

  • Insect Proteins
  • Protein Isoforms
  • Troponin C

Associated data

  • PDB/1J1D
  • PDB/1YTZ