{"doi":"10.1002/chem.202403608","title":"The Lassa Virus Stable Signal Peptide Undergoes a Conformational Change to Aid Viral Fusion","abstract":"A critical event in the lifecycle of the Lassa virus (LASV) is membrane fusion, where the viral membrane merges with the host cell membrane. This process is initiated by the LASV surface glycoprotein complex (GPC) upon exposure to the acidic environment of the endocytic pathway. A unique aspect of the GPC is the stable signal peptide (SSP), located adjacent to the transmembrane region of glycoprotein 2 (GP2), the primary fusion subunit. While previous research has established the importance of SSP in fusion, its precise role remains to be determined due to limited biophysical data. Our study aims to elucidate SSP's role by examining its structural changes. We discovered that SSP is predominantly α-helical in its prefusion state at pH 7. However, when the pH is lowered to mimic the late endosomal environment (<pH 5), SSP undergoes a structural change, increasing its helical content. Moreover, we demonstrate that SSP directly enhances fusion at these acidic pH levels. In conclusion, our findings suggest that SSP undergoes a critical conformational change at low pH, which is essential for its role in the LASV fusion mechanism, thereby deepening our understanding of LASV fusion.","journal":"Chemistry - A European Journal","year":2025,"id":551654,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1395914,"name":"Liqun Jiang","orcid":"0000-0002-8541-7539","position":1,"is_corresponding":false},{"id":1395915,"name":"Yanxin Liu","orcid":"0000-0001-5030-2435","position":2,"is_corresponding":false},{"id":653510,"name":"Jinwoo Lee","orcid":"0000-0002-1433-2810","position":3,"is_corresponding":false},{"id":1447728,"name":"Shane D. Collins","orcid":"0000-0002-9889-8984","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T02:54:29.318076Z","pmid":"39946735","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":[]}