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J Mol Biol. 2007 May 18;368(5):1426-37. Epub 2007 Mar 7.

Energetics-based protein profiling on a proteomic scale: identification of proteins resistant to proteolysis.

Author information

1
Department of Molecular and Cell Biology and QB3 Institute, University of California, Berkeley, Berkeley, CA 94720-3206, USA.

Abstract

Native states of proteins are flexible, populating more than just the unique native conformation. The energetics and dynamics resulting from this conformational ensemble are inherently linked to protein function and regulation. Proteolytic susceptibility is one feature determined by this conformational energy landscape. As an attempt to investigate energetics of proteins on a proteomic scale, we challenged the Escherichia coli proteome with extensive proteolysis and determined which proteins, if any, have optimized their energy landscape for resistance to proteolysis. To our surprise, multiple soluble proteins survived the challenge. Maltose binding protein, a survivor from thermolysin digestion, was characterized by in vitro biophysical studies to identify the physical origin of proteolytic resistance. This experimental characterization shows that kinetic stability is responsible for the unusual resistance in maltose binding protein. The biochemical functions of the identified survivors suggest that many of these proteins may have evolved extreme proteolytic resistance because of their critical roles under stressed conditions. Our results suggest that under functional selection proteins can evolve extreme proteolysis resistance by modulating their conformational energy landscapes without the need to invent new folds, and that proteins can be profiled on a proteomic scale according to their energetic properties by using proteolysis as a structural probe.

PMID:
17400245
PMCID:
PMC2857998
DOI:
10.1016/j.jmb.2007.02.091
[Indexed for MEDLINE]
Free PMC Article

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