Structural insights into SARS-CoV-2 nonstructural protein 4 (nsp4) biogenesis.

ABSTRACT: The SARS-CoV-2 virus-responsible for the COVID-19 pandemic-requires a replication-transcription complex (RTC) for efficient RNA synthesis and viral propagation. One critical RTC component is nonstructural protein 4 (nsp4), a multipass transmembrane (TM) protein implicated in endoplasmic reticulum (ER) membrane rearrangements and double-membrane vesicle (DMV) formation. The membrane topology and functional role of nsp4 in SARS-CoV-2 remain unclear. Here we determined that SARS-CoV-2 nsp4 contains a partially cleaved signal peptide, three TM segments, an extracellularly oriented N-terminus (towards the ER lumen in human cells), and a cytoplasm-facing C-terminus. The non-canonical glycosylation sequon (N¹³¹IC) in nsp4 is not glycosylated in mammalian cells. Molecular dynamics simul

SUBMITTER: Acosta-Caceres JM 

PROVIDER: S-EPMC12542298 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature