The Unfolding Journey of Superoxide Dismutase 1 Barrels Under Crowding: Atomistic Simulations Shed Light on Intermediate States and Their Interactions With Crowders
| Autor: | Simon Ebbinghaus, Stepan Timr, Fabio Sterpone, David Gnutt |
|---|---|
| Přispěvatelé: | Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Ruhr-Universität Bochum [Bochum], Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], This project has received funding from the European Union's Horizon 2020 research andinnovation programme under the Marie Sklodowska-Curie grant agreement No 840395., European Project: 840395,CROWDY, Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
macromolecular crowding
Light Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences thermal stability Superoxide dismutase 03 medical and health sciences Molecular dynamics Superoxide Dismutase-1 superoxide dismutase 1 Animals General Materials Science Physical and Theoretical Chemistry Bovine serum albumin 030304 developmental biology Protein Unfolding 0303 health sciences biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Chemistry Serum Albumin Bovine mutations 0104 chemical sciences [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics Excluded volume biology.protein Unfolded protein response Biophysics Thermodynamics Cattle molecular simulations Macromolecular crowding |
| Zdroj: | Journal of Physical Chemistry Letters Journal of Physical Chemistry Letters, 2020, ⟨10.1021/acs.jpclett.0c00699⟩ Journal of Physical Chemistry Letters, American Chemical Society, 2020, ⟨10.1021/acs.jpclett.0c00699⟩ The Journal of Physical Chemistry Letters |
| ISSN: | 1948-7185 |
| DOI: | 10.1021/acs.jpclett.0c00699⟩ |
| Popis: | International audience; The thermal stability of the superoxide dismutase 1 protein in a crowded solution is investigated by performing enhanced sampling molecular simulations. By complementing thermal unfolding experiments done close to physiological conditions (200 mg/mL), we provide evidence that the presence of the protein crowder bovine serum albumin in different packing states has only a minor, and essentially destabilizing, effect. The finding that quinary interactions counteract the pure stabilization contribution stemming from excluded volume is rationalized here by exploring the SOD1 unfolding mechanism in microscopic detail. In agreement with recent experiments, we unveil the importance of intermediate unfolded states as well as the correlation between protein conformations and local packing with the crowders. This link helps us to elucidate why certain SOD1 mutations involved in the ALS disease reverse the stability effect of the intracellular environment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|