Refolding SDS-denatured proteins by the addition of amphipathic cosolvents

J Mol Biol. 2008 Feb 1;375(5):1477-88. doi: 10.1016/j.jmb.2007.11.026. Epub 2007 Nov 19.

Abstract

Sodium dodecyl sulfate (SDS) is a highly effective and widely used protein denaturant. We show that certain amphipathic cosolvents such as 2-methyl-2,4-pentanediol (MPD) can protect proteins from SDS denaturation, and in several cases can refold proteins from the SDS-denatured state. This cosolvent effect is observed with integral membrane proteins and soluble proteins from either the alpha-helical or the beta-sheet structural classes. The SDS/MPD system can be used to study processes involving native protein states, and we demonstrate the reversible thermal denaturation of the outer membrane protein PagP in an SDS/MPD buffer. MPD and related cosolvents can modulate the denaturing properties of SDS, and we describe a simple and effective method to recover refolded, active protein from the SDS-denatured state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / metabolism
  • Animals
  • Bacterial Outer Membrane Proteins / isolation & purification
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacteriorhodopsins / chemistry
  • Buffers
  • Carbonic Anhydrase II / chemistry
  • Chickens
  • Dose-Response Relationship, Drug
  • Escherichia coli Proteins / metabolism
  • Glycols / chemistry
  • Halobacterium salinarum / chemistry
  • Hot Temperature
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Inclusion Bodies / chemistry
  • Muramidase / chemistry
  • Protein Conformation / drug effects
  • Protein Denaturation*
  • Protein Folding
  • Protein Renaturation*
  • Protein Structure, Secondary
  • Sodium Dodecyl Sulfate / pharmacology*
  • Solubility
  • Solvents / chemistry*
  • Surface-Active Agents / pharmacology*

Substances

  • Bacterial Outer Membrane Proteins
  • Buffers
  • Escherichia coli Proteins
  • Glycols
  • Solvents
  • Surface-Active Agents
  • Sodium Dodecyl Sulfate
  • Bacteriorhodopsins
  • Acyltransferases
  • PagP protein, E coli
  • Muramidase
  • Carbonic Anhydrase II
  • hexylene glycol