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Molecules. 2015 Jan 14;20(1):1377-409. doi: 10.3390/molecules20011377.

Beyond the excluded volume effects: mechanistic complexity of the crowded milieu.

Author information

1
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia. imk@mail.cytspb.rssi.ru.
2
Cleveland Diagnostics, 3615 Superior Ave., Suite 4407B, Cleveland, OH 44114, USA. Boris.Zaslavsky@Cleveland-Diagnostics.com.
3
Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33612, USA. lbreydo@health.usf.edu.
4
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia. kkt@incras.ru.
5
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia. vuversky@health.usf.edu.

Abstract

Macromolecular crowding is known to affect protein folding, binding of small molecules, interaction with nucleic acids, enzymatic activity, protein-protein interactions, and protein aggregation. Although for a long time it was believed that the major mechanism of the action of crowded environments on structure, folding, thermodynamics, and function of a protein can be described in terms of the excluded volume effects, it is getting clear now that other factors originating from the presence of high concentrations of "inert" macromolecules in crowded solution should definitely be taken into account to draw a more complete picture of a protein in a crowded milieu. This review shows that in addition to the excluded volume effects important players of the crowded environments are viscosity, perturbed diffusion, direct physical interactions between the crowding agents and proteins, soft interactions, and, most importantly, the effects of crowders on solvent properties.

PMID:
25594347
PMCID:
PMC6272634
DOI:
10.3390/molecules20011377
[Indexed for MEDLINE]
Free PMC Article

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