Reversible unfolding of fibronectin type III and immunoglobulin domains provides the structural basis for stretch and elasticity of titin and fibronectin

Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10114-8. doi: 10.1073/pnas.91.21.10114.

Abstract

The elastic protein titin comprises a tandem array of fibronectin type III and immunoglobulin domains, which are structurally similar 7-strand beta-sandwiches. A proposed mechanism for stretching titin, by sequential denaturation of individual fibronectin type III-immunoglobulin domains in response to applied tension, is analyzed here quantitatively. The folded domain is approximately 4 nm long, and the unraveled polypeptide can extend to 29 nm, providing a 7-fold stretch over the relaxed length. Elastic recoil is achieved by refolding of the denatured domains when the force is released. The critical force required to denature a domain is calculated to be 3.5-5 pN, based on a net free energy for denaturation of 7-14 kcal/mol, plus 5 kcal/mol to extend the polypeptide (1 cal = 4.184 J). This force is comparable to the 2- to 7-pN force generated by single myosin or kinesin molecules. The force needed to pull apart a noncovalent protein-protein interface is estimated here to be 10-30 pN, implying that titin will stretch internally before the molecule is pulled from its attachment at the Z band. Many extracellular matrix and cell adhesion molecules, such as fibronectin, contain tandem arrays of fibronectin type III domains. Both single molecules and matrix fibers should have elastic properties similar to titin.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calorimetry
  • Connectin
  • Elasticity
  • Fibronectins / chemistry*
  • Fibronectins / metabolism
  • Immunoglobulins / chemistry*
  • Kinesins / chemistry
  • Kinesins / metabolism
  • Membrane Proteins / chemistry
  • Models, Structural
  • Muscle Proteins / chemistry*
  • Muscle Proteins / metabolism
  • Myosins / chemistry
  • Myosins / metabolism
  • Protein Conformation*
  • Protein Denaturation
  • Protein Folding*
  • Protein Kinases*
  • Protein Structure, Secondary*

Substances

  • Connectin
  • Fibronectins
  • Immunoglobulins
  • Membrane Proteins
  • Muscle Proteins
  • Protein Kinases
  • Myosins
  • Kinesins