SARS-CoV-2 Spike Protein Downregulates Cell Surface α7nAChR through a Helical Motif in the Spike Neck.
ACS Chem Neurosci
; 14(4): 689-698, 2023 02 15.
Статья
в английский
| 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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Коллекция:
Международные базы данных
база данных:
MEDLINE
Основная тема:
Alpha7 Nicotinic Acetylcholine Receptor
/
COVID-19
Тип исследования:
Прогностическое исследование
Темы:
Длинный Ковид
/
Вакцина
Пределы темы:
Животные
/
Люди
Язык:
английский
Журнал:
ACS Chem Neurosci
Год:
2023
Тип:
Статья
Аффилированная страна:
Acschemneuro.2c00610
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