Unexpected effects of macromolecular crowding on protein stability

Biochemistry. 2012 Dec 11;51(49):9773-5. doi: 10.1021/bi300909q. Epub 2012 Nov 27.

Abstract

Most theories about macromolecular crowding focus on two ideas: the macromolecular nature of the crowder and entropy. For proteins, the volume excluded by the crowder favors compact native states over expanded denatured states, enhancing protein stability by decreasing the entropy of unfolding. We tested these ideas with the widely used crowding agent Ficoll-70 and its monomer, sucrose. Contrary to expectations, Ficoll and sucrose have approximately the same stabilizing effect on chymotrypsin inhibitor 2. Furthermore, the stabilization is driven by enthalpy, not entropy. These results point to the need for carefully controlled studies and more sophisticated theories for understanding crowding effects.

Publication types

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

MeSH terms

  • Macromolecular Substances / chemistry*
  • Proteins / chemistry*
  • Thermodynamics

Substances

  • Macromolecular Substances
  • Proteins