Time-resolved fluorescence resonance energy transfer study shows a compact denatured state of the B domain of protein A

Biochemistry. 2009 Apr 21;48(15):3468-76. doi: 10.1021/bi801890w.

Abstract

The B domain of protein A (BDPA), a three-helix bundle of 60 residues, folds via a nucleation-condensation mechanism in apparent two-state kinetics. We have applied a time-resolved FRET (tr-FRET) approach to characterize the ensembles of BDPA during chemical denaturation. The distribution of the distance between residues 22 and 55, which are close and separated by helices 2 and 3 in the native state, was determined by global analysis of the time-resolved fluorescence decay curves of the probes. Narrow distributions were observed when the protein was equilibrated in guanidinium chloride (GdmCl) concentrations below 1.5 M (native state, N) and above the transition zone at 2.6-3.0 M GdmCl (denatured state, D). Considerably broader distributions were found around the transition point (2.0 M GdmCl) or much higher GdmCl concentrations (>3.0 M). Comparative global analysis of the tr-FRET data showed a compact denatured state of the protein, characterized by narrow distribution and relatively small mean distance between residues 22 and 55 that was observed at mild denaturing conditions (<3 M GdmCl). This experiment supports the two-state folding mechanism of BDPA and indicates the existence of effective nonlocal, probably hydrophobic, intramolecular interactions that stabilize a pretty uniform ensemble of compact denatured molecules at intermediate denaturing conditions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Fluorescence Resonance Energy Transfer* / methods
  • Guanidine / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Protein Denaturation / genetics
  • Protein Folding
  • Protein Structure, Tertiary / genetics
  • Staphylococcal Protein A / chemistry*
  • Staphylococcal Protein A / genetics
  • Staphylococcal Protein A / metabolism*
  • Time Factors

Substances

  • Staphylococcal Protein A
  • Guanidine