Hydrogen-deuterium exchange strategy for delineation of contact sites in protein complexes

FEBS Lett. 2008 Apr 30;582(10):1495-500. doi: 10.1016/j.febslet.2008.03.043. Epub 2008 Apr 7.

Abstract

We use NMR spectra to determine protein-protein contact sites by observing differences in amide proton hydrogen-deuterium exchange in the complex compared to the free protein in solution. Aprotic organic solvents are used to preserve H/D labeling patterns that would be scrambled in water solutions. The binding site between the mammalian co-chaperone Aha1 with the middle domain of the chaperone Hsp90 obtained by our H/D exchange method corresponds well with that in the X-ray crystal structure of the homologous complex from yeast, even to the observation of a secondary binding site. This method can potentially provide data for complexes with unknown structure and for large or dynamic complexes inaccessible via NMR and X-ray methods.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Chaperonins
  • Deuterium / analysis
  • Deuterium / chemistry*
  • Dimethyl Sulfoxide / chemistry
  • HSP90 Heat-Shock Proteins / chemistry*
  • Humans
  • Hydrogen / analysis
  • Hydrogen / chemistry*
  • Molecular Chaperones / chemistry*
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Interaction Mapping / methods*
  • Protein Structure, Tertiary
  • Protons
  • Saccharomyces cerevisiae Proteins / chemistry
  • Solutions

Substances

  • AHA1 protein, S cerevisiae
  • AHSA1 protein, human
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • Protons
  • Saccharomyces cerevisiae Proteins
  • Solutions
  • Hydrogen
  • Deuterium
  • Chaperonins
  • Dimethyl Sulfoxide