The mechanical stability of ubiquitin is linkage dependent.

Journal Article, Research Support, U.S. Gov't, P.H.S.

Ubiquitin chains are formed through the action of a set of enzymes that covalently link ubiquitin either through peptide bonds or through isopeptide bonds between their C terminus and any of four lysine residues. These naturally occurring polyproteins allow one to study the mechanical stability of a protein, when force is applied through different linkages. Here we used single-molecule force spectroscopy techniques to examine the mechanical stability of N-C-linked and Lys48-C-linked ubiquitin chains. We combined these experiments with steered molecular dynamics (SMD) simulations and found that the mechanical stability and unfolding pathway of ubiquitin strongly depend on the linkage through which the mechanical force is applied to the protein. Hence, a protein that is otherwise very stable may be easily unfolded by a relatively weak mechanical force applied through the right linkage. This may be a widespread mechanism in biological systems.

Full Text

Duke Authors

Cited Authors

  • Carrion-Vazquez, M; Li, H; Lu, H; Marszalek, PE; Oberhauser, AF; Fernandez, JM

Published Date

  • September 2003

Published In

Volume / Issue

  • 10 / 9

Start / End Page

  • 738 - 743

PubMed ID

  • 12923571

International Standard Serial Number (ISSN)

  • 1072-8368

Digital Object Identifier (DOI)

  • 10.1038/nsb965

Language

  • eng

Citation Source

  • PubMed