tetano
Editor, Senior Moderator
Sci Rep
. 2024 Sep 11;14(1):21200.
doi: 10.1038/s41598-024-71144-5. SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions
Blanka Berta[SUP] 1 [/SUP], Hedvig Tordai[SUP] 1 [/SUP], Gergely L Lukács[SUP] 2 [/SUP], Béla Papp[SUP] 3 4 5 [/SUP], Ágnes Enyedi[SUP] 6 [/SUP], Rita Padányi[SUP] #[/SUP][SUP] 7 [/SUP], Tamás Hegedűs[SUP] #[/SUP][SUP] 8 9 [/SUP]
Affiliations
The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor; however, its role is poorly characterized. The E protein is a single-pass transmembrane protein that can assemble into a pentamer forming a viroporin, perturbing Ca[SUP]2+[/SUP] homeostasis. Because it is structurally similar to regulins such as, for example, phospholamban, that regulate the sarco/endoplasmic reticulum calcium ATPases (SERCA), we investigated whether the SARS-CoV-2 E protein affects the SERCA system as an exoregulin. Using FRET experiments we demonstrate that E protein can form oligomers with regulins, and thus can alter the monomer/multimer regulin ratio and consequently influence their interactions with SERCAs. We also confirm that a direct interaction between E protein and SERCA2b results in a decrease in SERCA-mediated ER Ca[SUP]2+[/SUP] reload. Structural modeling of the complexes indicates an overlapping interaction site for E protein and endogenous regulins. Our results reveal novel links in the host-virus interaction network that play an important role in viral pathogenesis and may provide a new therapeutic target for managing severe inflammatory responses induced by SARS-CoV-2.
Keywords: COVID-19; Ca2+ signaling; Envelope protein; Regulin; SARS-CoV-2; SERCA.
. 2024 Sep 11;14(1):21200.
doi: 10.1038/s41598-024-71144-5. SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions
Blanka Berta[SUP] 1 [/SUP], Hedvig Tordai[SUP] 1 [/SUP], Gergely L Lukács[SUP] 2 [/SUP], Béla Papp[SUP] 3 4 5 [/SUP], Ágnes Enyedi[SUP] 6 [/SUP], Rita Padányi[SUP] #[/SUP][SUP] 7 [/SUP], Tamás Hegedűs[SUP] #[/SUP][SUP] 8 9 [/SUP]
Affiliations
- PMID: 39261533
- DOI: 10.1038/s41598-024-71144-5
The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor; however, its role is poorly characterized. The E protein is a single-pass transmembrane protein that can assemble into a pentamer forming a viroporin, perturbing Ca[SUP]2+[/SUP] homeostasis. Because it is structurally similar to regulins such as, for example, phospholamban, that regulate the sarco/endoplasmic reticulum calcium ATPases (SERCA), we investigated whether the SARS-CoV-2 E protein affects the SERCA system as an exoregulin. Using FRET experiments we demonstrate that E protein can form oligomers with regulins, and thus can alter the monomer/multimer regulin ratio and consequently influence their interactions with SERCAs. We also confirm that a direct interaction between E protein and SERCA2b results in a decrease in SERCA-mediated ER Ca[SUP]2+[/SUP] reload. Structural modeling of the complexes indicates an overlapping interaction site for E protein and endogenous regulins. Our results reveal novel links in the host-virus interaction network that play an important role in viral pathogenesis and may provide a new therapeutic target for managing severe inflammatory responses induced by SARS-CoV-2.
Keywords: COVID-19; Ca2+ signaling; Envelope protein; Regulin; SARS-CoV-2; SERCA.