{"doi":"10.1101/2024.03.08.584019","title":"Cryo-EM inspired NMR analysis reveals a pH-induced conformational switching mechanism for imparting dynamics to Betanodavirus protrusions","abstract":"Abstract Nervous necrosis virus (NNV), a non-enveloped betanodavirus, causes neuropathies and retinopathies in farmed fish, damaging aquaculture worldwide. NNV has 60 conspicuous surface protrusions comprising the protrusion domain (P-domain) of its capsid protein. Although NNV protrusions play critical roles in infectivity, the underlying dynamics remain unclear. Our cryogenic electron microscopy (cryo-EM)-derived structures of Dragon grouper ( Epinephelus lanceolatus ) NNV reveal that the protrusions undergo low-pH-induced compaction and movement. We show that the P-domain is monomeric in solution at a pH germane to infection (7.0). Moreover, nuclear magnetic resonance (NMR) structures reveal a peptide (amino acids 311-330) that adopts a flexible loop to form an open pocket. NMR spectral analysis at pH 5.0 aided by molecular dynamics (MD) simulations show that this loop switches to a β-strand under acidic conditions, eliciting pocket closure and P-domain trimerization, highlighting a unique pH-sensing feature. Our docking analysis revealed the N-terminal moiety of sialic acid inserted into and interacting with conserved residues in the pocket. Additionally, a low-pH-induced conformational change in the linker region via peptide bond isomerization conferred malleability on the protrusions. Our work uncovers the protrusion dynamics of a betanodavirus governing its infectivity through a pH-dependent conformational switching mechanism, providing insights into complex virus-host interactions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490258,"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":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1335423,"name":"Chun-Hsiung Wang","orcid":"0000-0003-2242-7200","position":1,"is_corresponding":false},{"id":1335424,"name":"Kathleen Joyce Carillo","orcid":"0009-0006-1632-5709","position":2,"is_corresponding":false},{"id":327930,"name":"Yuan‐Chao Lou","orcid":null,"position":3,"is_corresponding":false},{"id":870949,"name":"Takayuki Kato","orcid":"0000-0002-8879-6685","position":4,"is_corresponding":false},{"id":1335425,"name":"Keiichi Namba","orcid":"0000-0003-2911-5875","position":5,"is_corresponding":false},{"id":1335426,"name":"Der‐Lii M. Tzou","orcid":"0000-0002-3755-8230","position":6,"is_corresponding":false},{"id":1335427,"name":"Wei‐Hau Chang","orcid":"0000-0002-2612-850X","position":7,"is_corresponding":false},{"id":1335422,"name":"Petra Štěrbová","orcid":"0000-0002-5300-6380","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:08:32.775003Z","pmid":null,"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":[]}