{"doi":"10.1371/journal.pbio.3000626","title":"Conformational changes in the Ebola virus membrane fusion machine induced by pH, Ca2+, and receptor binding","abstract":"The Ebola virus (EBOV) envelope glycoprotein (GP) is a membrane fusion machine required for virus entry into cells. Following endocytosis of EBOV, the GP1 domain is cleaved by cellular cathepsins in acidic endosomes, removing the glycan cap and exposing a binding site for the Niemann-Pick C1 (NPC1) receptor. NPC1 binding to cleaved GP1 is required for entry. How this interaction translates to GP2 domain-mediated fusion of viral and endosomal membranes is not known. Here, using a bulk fluorescence dequenching assay and single-molecule Förster resonance energy transfer (smFRET)-imaging, we found that acidic pH, Ca2+, and NPC1 binding synergistically induce conformational changes in GP2 and permit virus-liposome lipid mixing. Acidic pH and Ca2+ shifted the GP2 conformational equilibrium in favor of an intermediate state primed for NPC1 binding. Glycan cap cleavage on GP1 enabled GP2 to transition from a reversible intermediate to an irreversible conformation, suggestive of the postfusion 6-helix bundle; NPC1 binding further promoted transition to the irreversible conformation. Thus, the glycan cap of GP1 may allosterically protect against inactivation of EBOV by premature triggering of GP2.","journal":"PLoS Biology","year":2020,"id":55090,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":96,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":284586,"name":"Uriel Bulow","orcid":"0000-0003-4119-3171","position":1,"is_corresponding":false},{"id":284587,"name":"William E. Diehl","orcid":"0000-0001-7943-1214","position":2,"is_corresponding":false},{"id":284588,"name":"Natasha D. Durham","orcid":"0000-0003-0077-4770","position":3,"is_corresponding":false},{"id":284589,"name":"Fernando Senjobe","orcid":"0000-0003-4322-6571","position":4,"is_corresponding":false},{"id":109548,"name":"Kartik Chandran","orcid":"0000-0003-0232-7077","position":5,"is_corresponding":false},{"id":284590,"name":"Jeremy Luban","orcid":"0000-0001-5650-4054","position":6,"is_corresponding":false},{"id":284591,"name":"James B. Munro","orcid":"0000-0001-7634-4633","position":7,"is_corresponding":false},{"id":284585,"name":"Dibyendu Kumar Das","orcid":"0000-0002-8450-9298","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T21:04:59.506324Z","pmid":"32040508","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}