Discovery of a Thermophilic Protein Complex Stabilized by Topologically Interlinked Chains

Daniel R. Boutz, Duilio Cascio, Julian Whitelegge, L. Jeanne Perry, Todd O. Yeates

Research output: Contribution to journalArticlepeer-review

Abstract

A growing number of organisms have been discovered inhabiting extreme environments, including temperatures in excess of 100 °C. How cellular proteins from such organisms retain their native folds under extreme conditions is still not fully understood. Recent computational and structural studies have identified disulfide bonding as an important mechanism for stabilizing intracellular proteins in certain thermophilic microbes. Here, we present the first proteomic analysis of intracellular disulfide bonding in the hyperthermophilic archaeon Pyrobaculum aerophilum. Our study reveals that the utilization of disulfide bonds extends beyond individual proteins to include many protein-protein complexes. We report the 1.6 Å crystal structure of one such complex, a citrate synthase homodimer. The structure contains two intramolecular disulfide bonds, one per subunit, which result in the cyclization of each protein chain in such a way that the two chains are topologically interlinked, rendering them inseparable. This unusual feature emphasizes the variety and sophistication of the molecular mechanisms that can be achieved by evolution.

Original languageEnglish (US)
Pages (from-to)1332-1344
Number of pages13
JournalJournal of Molecular Biology
Volume368
Issue number5
DOIs
StatePublished - May 18 2007

Keywords

  • catenane
  • citrate synthase
  • disulfide bond
  • protein stability
  • thermophile

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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