NMR characterization of a "fibril-ready" state of demetalated wild-type superoxide dismutase

J Am Chem Soc. 2011 Jan 19;133(2):345-9. doi: 10.1021/ja1069689. Epub 2010 Dec 16.

Abstract

Demetalated superoxide dismutase (SOD1) is a transient species, fibrillogenic in nature and of biomedical interest. It is a conformationally disordered protein difficult to characterize. We have developed a strategy based on the NMR investigation of a crystalline species characterized by X-ray crystallography and on the comparison of the solid-state-solution-state chemical shifts. The solid-state assignment has been also helpful in assigning the solution spectra. The solution NMR spectra presumably detect species that are the result of equilibria among multiple species. From the differences in chemical shifts between the two forms, we learned that a β-sheet becomes conformationally labile and two loops in the same sheet show propensity to take a β conformation. This strategy, which exploits solution and solid-state NMR spectra in a synergistic way, thus provides information on the species that are prone to oligomerize.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular*
  • Protein Conformation
  • Superoxide Dismutase / chemistry*
  • Superoxide Dismutase / metabolism

Substances

  • Superoxide Dismutase