title: The crowd you're in with: effects of different types of crowding agents on protein aggregation.
abstract: The intracellular environment contains high concentrations of macromolecules occupying up to 30% of the total cellular volume. Presence of these macromolecules decreases the effective volume available for the proteins in the cell and thus increases the effective protein concentrations and stabilizes the compact protein conformations. Macromolecular crowding created by various macromolecules such as proteins, nucleic acids, and carbohydrates has been shown to have a significant effect on a variety of cellular processes including protein aggregation. Most studies of macromolecular crowding have used neutral, flexible polysaccharides that function primarily via excluded volume effect as model crowding agents. Here we have examined the effects of more rigid polysaccharides on protein structure and aggregation. Our results indicate that rigid and flexible polysaccharides influence protein aggregation via different mechanisms and suggest that, in addition to excluded volume effect, changes in solution viscosity and non-specific protein-polymer interactions influence the structure and dynamics of proteins in crowded environments.
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. Electronic address: lbreydo@health.usf.edu.
authors.forename: Leonid
authors.initials: L
authors.lastname: Breydo
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Krishna D
authors.initials: KD
authors.lastname: Reddy
authors.affiliation: Center for Magnetic Resonance, University of Florence, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piai
authors.affiliation: Center for Magnetic Resonance, University of Florence, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Isabella C
authors.initials: IC
authors.lastname: Felli
authors.affiliation: Center for Magnetic Resonance, University of Florence, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pierattelli
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; Institute for Biological Instrumentation, Russian Academy of Sciences, 142292 Pushchino, Moscow Region, Russia. Electronic address: vuversky@health.usf.edu.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D002482:Cellulose / Q000031:analogs & derivatives / Q000494:pharmacology; D011232:Chemical Precipitation / Q000187:drug effects*; D003911:Dextrans / Q000494:pharmacology; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D003911:Dextrans; D006657:Histones; D007328:Insulin; D011134:Polysaccharides; D051844:alpha-Synuclein; D002482:Cellulose; C008079:hydroxypropylcellulose; D009113:Muramidase
keywords: Amyloid; Crowding; Flexibility; Intrinsic disorder; Protein aggregation