ArticleProceedings of the National Academy of Sciences of the United States of America2013
Probing the transient dark state of substrate binding to GroEL by relaxation-based solution NMR.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
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- Quantitative NMR analysis of the mechanism and kinetics of chaperone Hsp104 action on amyloid-β42 aggregation and fibril formation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- New Paradigm for Nano-Bio Interactions: Multimolecular Assembly of a Prototypical Disordered Protein with Ultrasmall Nanoparticles.Nano letters · 2022Article
- Global Dynamics of a Protein on the Surface of Anisotropic Lipid Nanoparticles Derived from Relaxation-Based NMR Spectroscopy.The journal of physical chemistry. B · 2022Article
- Solution NMR methods for structural and thermodynamic investigation of nanoparticle adsorption equilibria.Nanoscale advances · 2022Review
- Large Chaperone Complexes Through the Lens of Nuclear Magnetic Resonance Spectroscopy.Annual review of biophysics · 2022Review
- Reversible Kinetic Trapping of FUS Biomolecular Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- NMR methods for exploring 'dark' states in ligand binding and protein-protein interactions.Progress in nuclear magnetic resonance spectroscopy · 2022Review
- Unveiling an NMR-Invisible Fraction of Polymers in Solution by Saturation Transfer Difference.ACS macro letters · 2021Article
- Quantitative NMR Study of Insulin-Degrading Enzyme Using Amyloid-β and HIV-1 p6 Elucidates Its Chaperone Activity.Biochemistry · 2021Article
- Probing the Interaction of Huntingtin Exon-1 Polypeptides with the Chaperonin Nanomachine GroEL.Chembiochem : a European journal of chemical biology · 2021Article
- Molecular chaperones and their denaturing effect on client proteins.Journal of biomolecular NMR · 2021Article
- The (un)structural biology of biomolecular liquid-liquid phase separation using NMR spectroscopy.The Journal of biological chemistry · 2020Review
- NMR Methods for Structural Characterization of Protein-Protein Complexes.Frontiers in molecular biosciences · 2020Article
- NMR Lineshape Analysis of Intrinsically Disordered Protein Interactions.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Protein Interactions with Nanoparticle Surfaces: Highlighting Solution NMR Techniques.Israel journal of chemistry · 2019Article
- Unraveling the structure and dynamics of the human DNAJB6b chaperone by NMR reveals insights into Hsp40-mediated proteostasis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Exchange saturation transfer and associated NMR techniques for studies of protein interactions involving high-molecular-weight systems.Journal of biomolecular NMR · 2019Article
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Abstract
The mechanism whereby the prototypical chaperonin GroEL performs work on substrate proteins has not yet been fully elucidated, hindered by lack of detailed structural and dynamic information on the bound substrate. Previous investigations have produced conflicting reports on the state of GroEL-bound polypeptides, largely due to the transient and dynamic nature of these complexes. Here, we present a unique approach, based on combined analysis of four complementary relaxation-based NMR experiments, to probe directly the "dark" NMR-invisible state of the model, intrinsically disordered, polypeptide amyloid β (Aβ40) bound to GroEL. The four NMR experiments, lifetime line-broadening, dark-state exchange saturation transfer, relaxation dispersion, and small exchange-induced chemical shifts, are dependent in different ways on the overall exchange rates and populations of the free and bound states of the substrate, as well as on residue-specific dynamics and structure within the bound state as reported by transverse magnetization relaxation rates and backbone chemical shifts, respectively. Global fitting of all the NMR data shows that the complex is transient with a lifetime of <1 ms, that binding involves two predominantly hydrophobic segments corresponding to predicted GroEL consensus binding sequences, and that the structure of the bound polypeptide remains intrinsically and dynamically disordered with minimal changes in secondary structure propensity relative to the free state. Our results establish a unique method to observe NMR-invisible dynamic states of GroEL-bound substrates and to describe at atomic resolution the events between substrate binding and encapsulation that are crucial for understanding the normal and stress-related metabolic function of chaperonins.
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