The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization
The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC),...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/171023 |
| _version_ | 1826120477100212224 |
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| author | Surya, Wahyu Tavares-Neto, Ernesto Sanchis, Andrea Queralt-Martín, María Alcaraz, Antonio Torres, Jaume Aguilella, Vicente M. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Surya, Wahyu Tavares-Neto, Ernesto Sanchis, Andrea Queralt-Martín, María Alcaraz, Antonio Torres, Jaume Aguilella, Vicente M. |
| author_sort | Surya, Wahyu |
| collection | NTU |
| description | The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), where virion budding takes place. Several reports claim that E protein promotes the formation of "cation-selective channels". However, whether this term represents specificity to certain ions (e.g., potassium or calcium) or the partial or total exclusion of anions is debatable. Herein, we discuss this claim based on the available data for SARS-CoV-1 and -2 E and on new experiments performed using the untagged full-length E protein from SARS-CoV-2 in planar lipid membranes of different types, including those that closely mimic the ERGIC membrane composition. We provide evidence that the selectivity of the E-induced channels is very mild and depends strongly on lipid environment. Thus, despite past and recent claims, we found no indication that the E protein forms cation-selective channels that prevent anion transport, and even less that E protein forms bona fide specific calcium channels. In fact, the E channel maintains its multi-ionic non-specific neutral character even in concentrated solutions of Ca2+ ions. Also, in contrast to previous studies, we found no evidence that SARS-CoV-2 E channel activation requires a particular voltage, high calcium concentrations or low pH, in agreement with available data from SARS-CoV-1 E. In addition, sedimentation velocity experiments suggest that the E channel population is mostly pentameric, but very dynamic and probably heterogeneous, consistent with the broad distribution of conductance values typically found in electrophysiological experiments. The latter has been explained by the presence of proteolipidic channel structures. |
| first_indexed | 2024-10-01T05:17:06Z |
| format | Journal Article |
| id | ntu-10356/171023 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:17:06Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1710232023-10-16T15:32:36Z The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization Surya, Wahyu Tavares-Neto, Ernesto Sanchis, Andrea Queralt-Martín, María Alcaraz, Antonio Torres, Jaume Aguilella, Vicente M. School of Biological Sciences Science::Biological sciences Analytical Ultracentrifugation Envelope Protein The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), where virion budding takes place. Several reports claim that E protein promotes the formation of "cation-selective channels". However, whether this term represents specificity to certain ions (e.g., potassium or calcium) or the partial or total exclusion of anions is debatable. Herein, we discuss this claim based on the available data for SARS-CoV-1 and -2 E and on new experiments performed using the untagged full-length E protein from SARS-CoV-2 in planar lipid membranes of different types, including those that closely mimic the ERGIC membrane composition. We provide evidence that the selectivity of the E-induced channels is very mild and depends strongly on lipid environment. Thus, despite past and recent claims, we found no indication that the E protein forms cation-selective channels that prevent anion transport, and even less that E protein forms bona fide specific calcium channels. In fact, the E channel maintains its multi-ionic non-specific neutral character even in concentrated solutions of Ca2+ ions. Also, in contrast to previous studies, we found no evidence that SARS-CoV-2 E channel activation requires a particular voltage, high calcium concentrations or low pH, in agreement with available data from SARS-CoV-1 E. In addition, sedimentation velocity experiments suggest that the E channel population is mostly pentameric, but very dynamic and probably heterogeneous, consistent with the broad distribution of conductance values typically found in electrophysiological experiments. The latter has been explained by the presence of proteolipidic channel structures. Ministry of Education (MOE) Published version This research was funded by grants awarded to J.T. by the Singapore Ministry of Education (MOE) Tier 1 grant RG92/21. A.A. and V.M.A. acknowledge funding by the Spanish Government MCIN/AEI/10.13039/501100011033 (project 2019-108434GB-I00) and Universitat Jaume I (project UJI-B2022-42). 2023-10-10T05:51:23Z 2023-10-10T05:51:23Z 2023 Journal Article Surya, W., Tavares-Neto, E., Sanchis, A., Queralt-Martín, M., Alcaraz, A., Torres, J. & Aguilella, V. M. (2023). The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization. International Journal of Molecular Sciences, 24(15), 12454-. https://dx.doi.org/10.3390/ijms241512454 1661-6596 https://hdl.handle.net/10356/171023 10.3390/ijms241512454 37569828 2-s2.0-85167739394 15 24 12454 en RG92/21 International Journal of Molecular Sciences © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). application/pdf |
| spellingShingle | Science::Biological sciences Analytical Ultracentrifugation Envelope Protein Surya, Wahyu Tavares-Neto, Ernesto Sanchis, Andrea Queralt-Martín, María Alcaraz, Antonio Torres, Jaume Aguilella, Vicente M. The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization |
| title | The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization |
| title_full | The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization |
| title_fullStr | The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization |
| title_full_unstemmed | The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization |
| title_short | The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: weak selectivity and heterogeneous oligomerization |
| title_sort | complex proteolipidic behavior of the sars cov 2 envelope protein channel weak selectivity and heterogeneous oligomerization |
| topic | Science::Biological sciences Analytical Ultracentrifugation Envelope Protein |
| url | https://hdl.handle.net/10356/171023 |
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