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SARS-CoV-2 Spike Protein Downregulates Cell Surface α7nAChR through a Helical Motif in the Spike Neck.
Tillman, Tommy S; Chen, Qiang; Bondarenko, Vasyl; Coleman, Jonathan A; Xu, Yan; Tang, Pei.
  • Tillman TS; Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
  • Chen Q; Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
  • Bondarenko V; Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
  • Coleman JA; Department of Structural Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
  • Xu Y; Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
  • Tang P; Department of Structural Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
ACS Chem Neurosci ; 14(4): 689-698, 2023 02 15.
Article in English | MEDLINE | ID: covidwho-2236297
ABSTRACT
A deficiency of the functional α7 nicotinic acetylcholine receptor (α7nAChR) impairs neuronal and immune systems. The SARS-CoV-2 spike protein (S12) facilitates virus cell entry during COVID-19 infection and can also independently disrupt cellular functions. Here, we found that S12 expression significantly downregulated surface expression of α7nAChR in mammalian cells. A helical segment of S12 (L1145-L1152) in the spike neck was identified to be responsible for the downregulation of α7nAChR, as the mutant S12AAA (L1145A-F1148A-L1152A) had minimal effects on surface α7nAChR expression. This S12 segment is homologous to the α7nAChR intracellular helical motif known for binding chaperone proteins RIC3 and Bcl-2 to promote α7nAChR surface expression. Competition from S12 for binding these proteins likely underlies suppression of surface α7nAChR. Considering the critical roles of α7nAChR in cellular functions, these findings provide a new perspective for improving mRNA vaccines and developing treatment options for certain symptoms related to long COVID.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Alpha7 Nicotinic Acetylcholine Receptor / COVID-19 Type of study: Prognostic study Topics: Long Covid / Vaccines Limits: Animals / Humans Language: English Journal: ACS Chem Neurosci Year: 2023 Document Type: Article Affiliation country: Acschemneuro.2c00610

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Alpha7 Nicotinic Acetylcholine Receptor / COVID-19 Type of study: Prognostic study Topics: Long Covid / Vaccines Limits: Animals / Humans Language: English Journal: ACS Chem Neurosci Year: 2023 Document Type: Article Affiliation country: Acschemneuro.2c00610