Protein self-association induced by macromolecular crowding: A quantitative analysis by magnetic relaxation dispersion
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/151522
- author
- Snoussi, Karim LU and Halle, Bertil LU
- organization
- publishing date
- 2005
- 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
- pmid:15665132
- 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
- 2016-04-01 11:49:26
- date last changed
- 2022-01-26 18:46:53
@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}},
doi = {{10.1529/biophysj.104.055871}},
volume = {{88}},
year = {{2005}},
}