ArticleJournal of the American Chemical Society2010
Macromolecular crowding remodels the energy landscape of a protein by favoring a more compact unfolded state.
Article in Journal of the American Chemical Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 177 citations in OpenAlex.
- Crowder-specific modulation of hepatitis C virus NS3/4A protease activity and local structural dynamics.Protein science : a publication of the Protein Society · 2026Article
- Therapeutic Potential of Solanum macrocarpon in Uterine Leiomyoma: In Vivo and In Silico Approaches.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Mechanistic insights into how water-network disorder determines the vitrification concentration in cryopreservation solutions.Cell reports. Physical science · 2026Article
- Aggregation of Phosphates Enhances Enzyme Activity in Aqueous Solution.Chemphyschem : a European journal of chemical physics and physical chemistry · 2026Article
- Small heat shock proteins and biomolecular condensates.Cellular and molecular life sciences : CMLS · 2026Review
- Water Under Molecular Crowding: From Femtosecond H-Bond Networks Dynamics to Biological Function.Sub-cellular biochemistry · 2026Review
- Capturing Structure and Morphology in Responsive Microgels: From Intrinsic Free Energy to Collective Behavior.Macromolecules · 2025Article
- A coarse-grained model for disordered proteins under crowded conditions.Protein science : a publication of the Protein Society · 2025Article
- Role of Aqueous Media in Macromolecular Crowding.Sub-cellular biochemistry · 2025Review
- Ethnomedicinal validation ofFrontiers in nutrition · 2025Article
- Unfolding Mechanism and Fibril Formation Propensity of Human Prion Protein in the Presence of Molecular Crowding Agents.International journal of molecular sciences · 2024Article
- Effects of Macromolecular Cosolutes on the Kinetics of Huntingtin Aggregation Monitored by NMR Spectroscopy.The journal of physical chemistry letters · 2024Article
- Computational Approaches to Predict Protein-Protein Interactions in Crowded Cellular Environments.Chemical reviews · 2024Review
- Conformational fluctuations and phases in fused in sarcoma (FUS) low-complexity domain.Biopolymers · 2024Review
- In silico protein dynamics in the human cytoplasm: Partial folding, misfolding, fold switching, and non-native interactions.Protein science : a publication of the Protein Society · 2023Article
- Simulations of a protein fold switch reveal crowding-induced population shifts driven by disordered regions.Communications chemistry · 2023Article
- Crowded environments tune the fold-switching in metamorphic proteins.Communications chemistry · 2023Article
- Article
- Molecular mechanisms of steric pressure generation and membrane remodeling by disordered proteins.Biophysical journal · 2022Article
- Crowding-induced protein destabilization in the absence of soft attractions.Biophysical journal · 2022Article
14 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
The interior of cells is highly crowded with macromolecules, which impacts all physiological processes. To explore how macromolecular crowding may influence cellular protein folding, we interrogated the folding landscape of a model beta-rich protein, cellular retinoic acid-binding protein I (CRABP I), in the presence of an inert crowding agent (Ficoll 70). Urea titrations revealed a crowding-induced change in the water-accessible polar amide surface of its denatured state, based on an observed ca. 15% decrease in the change in unfolding free energy with respect to urea concentration (the m-value), and the effect of crowding on the equilibrium stability of CRABP I was less than our experimental error (i.e., < or = 1.2 kcal/mol). Consequently, we directly probed the effect of crowding on the denatured state of CRABP I by measuring side-chain accessibility using iodide quenching of tryptophan fluorescence and chemical modification of cysteines. We observed that the urea-denatured state is more compact under crowded conditions, and the observed extent of reduction of the m-value by crowding agent is fully consistent with the extent of reduction of the accessibility of the Trp and Cys probes, suggesting a random and nonspecific compaction of the unfolded state. The thermodynamic consequences of crowding-induced compaction are discussed. In addition, over a wide range of Ficoll concentration, crowding significantly retarded the unfolding kinetics of CRABP I without influencing the urea dependence of the unfolding rate, arguing for no appreciable change in the nature of the transition state. Our results demonstrate how macromolecular crowding may influence protein folding by effects on both the unfolded state ensemble and unfolding kinetics.
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