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Protein self-association induced by macromolecular crowding: A quantitative analysis by magnetic relaxation dispersion

Snoussi, Karim LU and Halle, Bertil LU (2005) In Biophysical Journal 88(4). p.2855-2866
Abstract
In the presence of high concentrations of inert macromolecules, the self-association of proteins is strongly enhanced through an entropic, excluded-volume effect variously called macromolecular crowding or depletion attraction. Despite the predicted large magnitude of this universal effect and its far-reaching biological implications, few experimental studies of macromolecular crowding have been reported. Here, we introduce a powerful new technique, fast field-cycling magnetic relaxation dispersion, for investigating crowding effects on protein self-association equilibria. By recording the solvent proton spin relaxation rate over a wide range of magnetic field strengths, we determine the populations of coexisting monomers and decamers of... (More)
In the presence of high concentrations of inert macromolecules, the self-association of proteins is strongly enhanced through an entropic, excluded-volume effect variously called macromolecular crowding or depletion attraction. Despite the predicted large magnitude of this universal effect and its far-reaching biological implications, few experimental studies of macromolecular crowding have been reported. Here, we introduce a powerful new technique, fast field-cycling magnetic relaxation dispersion, for investigating crowding effects on protein self-association equilibria. By recording the solvent proton spin relaxation rate over a wide range of magnetic field strengths, we determine the populations of coexisting monomers and decamers of bovine pancreatic trypsin inhibitor in the presence of dextran up to a macromolecular volume fraction of 27%. Already at a dextran volume fraction of 14%, we find a 30-fold increase of the decamer population and 510(5)-fold increase of the association constant. The analysis of these results, in terms of a statistical-mechanical model that incorporates polymer flexibility as well as the excluded volume of the protein, shows that the dramatic enhancement of bovine pancreatic trypsin inhibitor self-association can be quantitatively rationalized in terms of hard repulsive interactions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biophysical Journal
volume
88
issue
4
pages
2855 - 2866
publisher
Cell Press
external identifiers
  • pmid:15665132
  • wos:000227986300044
  • scopus:22144435939
ISSN
1542-0086
DOI
10.1529/biophysj.104.055871
language
English
LU publication?
yes
id
0884e4f0-09a8-4140-b663-0e09321697c4 (old id 151522)
date added to LUP
2007-06-29 14:23:51
date last changed
2017-09-03 03:41:00
@article{0884e4f0-09a8-4140-b663-0e09321697c4,
  abstract     = {In the presence of high concentrations of inert macromolecules, the self-association of proteins is strongly enhanced through an entropic, excluded-volume effect variously called macromolecular crowding or depletion attraction. Despite the predicted large magnitude of this universal effect and its far-reaching biological implications, few experimental studies of macromolecular crowding have been reported. Here, we introduce a powerful new technique, fast field-cycling magnetic relaxation dispersion, for investigating crowding effects on protein self-association equilibria. By recording the solvent proton spin relaxation rate over a wide range of magnetic field strengths, we determine the populations of coexisting monomers and decamers of bovine pancreatic trypsin inhibitor in the presence of dextran up to a macromolecular volume fraction of 27%. Already at a dextran volume fraction of 14%, we find a 30-fold increase of the decamer population and 510(5)-fold increase of the association constant. The analysis of these results, in terms of a statistical-mechanical model that incorporates polymer flexibility as well as the excluded volume of the protein, shows that the dramatic enhancement of bovine pancreatic trypsin inhibitor self-association can be quantitatively rationalized in terms of hard repulsive interactions.},
  author       = {Snoussi, Karim and Halle, Bertil},
  issn         = {1542-0086},
  language     = {eng},
  number       = {4},
  pages        = {2855--2866},
  publisher    = {Cell Press},
  series       = {Biophysical Journal},
  title        = {Protein self-association induced by macromolecular crowding: A quantitative analysis by magnetic relaxation dispersion},
  url          = {http://dx.doi.org/10.1529/biophysj.104.055871},
  volume       = {88},
  year         = {2005},
}