Reverse engineering of the giant muscle protein titin

Nature. 2002 Aug 29;418(6901):998-1002. doi: 10.1038/nature00938.

Abstract

Through the study of single molecules it has become possible to explain the function of many of the complex molecular assemblies found in cells. The protein titin provides muscle with its passive elasticity. Each titin molecule extends over half a sarcomere, and its extensibility has been studied both in situ and at the level of single molecules. These studies suggested that titin is not a simple entropic spring but has a complex structure-dependent elasticity. Here we use protein engineering and single-molecule atomic force microscopy to examine the mechanical components that form the elastic region of human cardiac titin. We show that when these mechanical elements are combined, they explain the macroscopic behaviour of titin in intact muscle. Our studies show the functional reconstitution of a protein from the sum of its parts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Connectin
  • Elasticity
  • Entropy
  • Humans
  • Microscopy, Atomic Force*
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle Proteins / ultrastructure*
  • Myocardium / chemistry
  • Myocardium / ultrastructure
  • Protein Engineering*
  • Protein Folding
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Kinases / ultrastructure*

Substances

  • Connectin
  • Muscle Proteins
  • TTN protein, human
  • Protein Kinases