Flavivirus Zika NS4A protein forms large oligomers in liposomes and in mild detergent.
Sci Rep
; 14(1): 12533, 2024 05 31.
Article
en En
| MEDLINE
| ID: mdl-38822066
ABSTRACT
In flaviviruses such as Dengue or Zika, non-structural (NS) NS4A protein forms homo-oligomers, participates in membrane remodelling and is critical for virulence. In both viruses, mature NS4A has the same length and three predicted hydrophobic domains. The oligomers formed by Dengue NS4A are reported to be small (n = 2, 3), based on denaturing SDS gels, but no high-resolution structure of a flavivirus NS4A protein is available, and the size of the oligomer in lipid membranes is not known. Herein we show that crosslinking Zika NS4A protein in lipid membranes results in oligomers at least up to hexamers. Further, sedimentation velocity shows that NS4A in mild detergent C14-betaine appears to be in fast equilibrium between at least two species, where one is smaller, and the other larger, than a trimer or a tetramer. Consistently, sedimentation equilibrium data was best fitted to a model involving an equilibrium between dimers (n = 2) and hexamers (n = 6). Overall, the large, at least hexameric, oligomers obtained herein in liposomes and in mild detergent are more likely to represent the forms of NS4A present in cell membranes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas no Estructurales Virales
/
Detergentes
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Multimerización de Proteína
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Virus Zika
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Liposomas
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Singapur
Pais de publicación:
Reino Unido