A second look at mini-protein stability: analysis of FSD-1 using circular dichroism, differential scanning calorimetry, and simulations

Biophys J. 2009 Nov 18;97(10):2803-10. doi: 10.1016/j.bpj.2009.08.046.

Abstract

Mini-proteins that contain <50 amino acids often serve as model systems for studying protein folding because their small size makes long timescale simulations possible. However, not all mini-proteins are created equal. The stability and structure of FSD-1, a 28-residue mini-protein that adopted the betabetaalpha zinc-finger motif independent of zinc binding, was investigated using circular dichroism, differential scanning calorimetry, and replica-exchange molecular dynamics. The broad melting transition of FSD-1, similar to that of a helix-to-coil transition, was observed by using circular dichroism, differential scanning calorimetry, and replica-exchange molecular dynamics. The N-terminal beta-hairpin was found to be flexible. The FSD-1 apparent melting temperature of 41 degrees C may be a reflection of the melting of its alpha-helical segment instead of the entire protein. Thus, despite its attractiveness due to small size and purposefully designed helix, sheet, and turn structures, the status of FSD-1 as a model system for studying protein folding should be reconsidered.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning
  • Circular Dichroism
  • Computer Simulation
  • DNA-Binding Proteins / chemistry*
  • Hydrogen Bonding
  • Models, Chemical
  • Models, Molecular
  • Phase Transition
  • Protein Folding
  • Protein Stability
  • Protein Structure, Secondary
  • Temperature
  • Transcription Factors / chemistry*
  • Transition Temperature

Substances

  • DNA-Binding Proteins
  • FSD-1 protein, synthetic
  • Transcription Factors