The mechanical stability of ubiquitin is linkage dependent

Mariano Carrion-Vazquez, Hongbin Li, Hui Lu, Piotr E. Marszalek, Andres F. Oberhauser, Julio M. Fernandez

Research output: Contribution to journalArticle

349 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)738-743
Number of pages6
JournalNature Structural Biology
Volume10
Issue number9
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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    Carrion-Vazquez, M., Li, H., Lu, H., Marszalek, P. E., Oberhauser, A. F., & Fernandez, J. M. (2003). The mechanical stability of ubiquitin is linkage dependent. Nature Structural Biology, 10(9), 738-743. https://doi.org/10.1038/nsb965