The mechanical stability of ubiquitin is linkage dependent

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

Research output: Contribution to journalArticle

343 Citations (Scopus)

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

Fingerprint

Mechanical stability
Ubiquitin
Ubiquitin C
Polyproteins
Protein Stability
Molecular Dynamics Simulation
Proteins
Lysine
Biological systems
Molecular dynamics
Peptides
Spectroscopy
Enzymes
Molecules
Computer simulation
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Carrion-Vazquez, M., Li, H., Lu, H., Marszalek, P. E., Oberhauser, A., & 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

The mechanical stability of ubiquitin is linkage dependent. / Carrion-Vazquez, Mariano; Li, Hongbin; Lu, Hui; Marszalek, Piotr E.; Oberhauser, Andres; Fernandez, Julio M.

In: Nature Structural Biology, Vol. 10, No. 9, 01.09.2003, p. 738-743.

Research output: Contribution to journalArticle

Carrion-Vazquez, M, Li, H, Lu, H, Marszalek, PE, Oberhauser, A & Fernandez, JM 2003, 'The mechanical stability of ubiquitin is linkage dependent', Nature Structural Biology, vol. 10, no. 9, pp. 738-743. https://doi.org/10.1038/nsb965
Carrion-Vazquez M, Li H, Lu H, Marszalek PE, Oberhauser A, Fernandez JM. The mechanical stability of ubiquitin is linkage dependent. Nature Structural Biology. 2003 Sep 1;10(9):738-743. https://doi.org/10.1038/nsb965
Carrion-Vazquez, Mariano ; Li, Hongbin ; Lu, Hui ; Marszalek, Piotr E. ; Oberhauser, Andres ; Fernandez, Julio M. / The mechanical stability of ubiquitin is linkage dependent. In: Nature Structural Biology. 2003 ; Vol. 10, No. 9. pp. 738-743.
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