{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Acosta-Caceres JM"],"funding":["Deutsche Forschungsgemeinschaft","Spanish Ministry of Science and Innovation","Generalitat Valenciana"],"pagination":["e70355"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12542298"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["34(11)"],"pubmed_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 (N<sup>131</sup>IC) in nsp4 is not glycosylated in mammalian cells. Molecular dynamics simul"],"journal":["Protein science : a publication of the Protein Society"],"pubmed_title":["Structural insights into SARS-CoV-2 nonstructural protein 4 (nsp4) biogenesis."],"pmcid":["PMC12542298"],"funding_grant_id":["PID2023-152568NB-I00","SFB-1638/1-511488495-Z01","PID2020-119111GB-I00","CIPROM/2022/062"],"pubmed_authors":["Acosta-Caceres JM","Mingarro I","Garcia-Murria MJ","Martinez-Gil L","Ortiz-Mateu J","Gadea-Salom L","Lolicato F","Belda D"],"additional_accession":[]},"is_claimable":false,"name":"Structural insights into SARS-CoV-2 nonstructural protein 4 (nsp4) biogenesis.","description":"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 (N<sup>131</sup>IC) in nsp4 is not glycosylated in mammalian cells. Molecular dynamics simul","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-07-15T07:00:36.322Z","creation":"2026-07-02T03:08:24.561Z"},"accession":"S-EPMC12542298","cross_references":{"pubmed":["41123415"],"doi":["10.1002/pro.70355"]}}