{"doi":"10.1073/pnas.2315733121","title":"The structure of a <i>Cryptococcus neoformans</i> polysaccharide motif recognized by protective antibodies: A combined NMR and MD study","abstract":"Cryptococcus neoformans is a fungal pathogen responsible for cryptococcosis and cryptococcal meningitis. The C. neoformans ’ capsular polysaccharide and its shed exopolysaccharide function both as key virulence factors and to protect the fungal cell from phagocytosis. Currently, a glycoconjugate of these polysaccharides is being explored as a vaccine to protect against C. neoformans infection. In this study, NOE and J -coupling values from NMR experiments were consistent with a converged structure of the synthetic decasaccharide, GXM10-Ac 3 , calculated from MD simulations. GXM10-Ac 3 was designed as an extension of glucuronoxylomannan (GXM) polysaccharide motif (M2) which is common in the clinically predominant serotype A strains and is recognized by protective forms of GXM-specific monoclonal antibodies. The M2 motif is a hexasaccharide with a three-residue α-mannan backbone, modified by β-(1→2)-xyloses (Xyl) on the first two mannoses (Man) and a β-(1→2)-glucuronic acid (GlcA) on the third Man. Combined NMR and MD analyses reveal that GXM10-Ac 3 adopts an extended structure, with Xyl/GlcA branches alternating sides along the α-mannan backbone. O -acetyl esters also alternate sides and are grouped in pairs. MD analysis of a twelve M2-repeating unit polymer supports the notion that the GXM10-Ac 3 structure is uniformly represented throughout the polysaccharide. This derived GXM model displays high flexibility while maintaining a structural identity, yielding insights to further explore intermolecular interactions between polysaccharides, interactions with anti-GXM mAbs, and the cryptococcal polysaccharide architecture.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":437784,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"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":1172817,"name":"Hugo F. Azurmendi","orcid":"0000-0002-5773-9127","position":1,"is_corresponding":false},{"id":466144,"name":"C. Crawford","orcid":"0000-0002-1314-1019","position":2,"is_corresponding":false},{"id":466146,"name":"Maggie P. Wear","orcid":"0000-0002-8581-7831","position":3,"is_corresponding":false},{"id":413872,"name":"Stefan Oscarson","orcid":"0000-0002-8273-4918","position":4,"is_corresponding":false},{"id":107237,"name":"Arturo Casadevall","orcid":"0000-0002-9402-9167","position":5,"is_corresponding":false},{"id":397970,"name":"Darón I. Freedberg","orcid":"0000-0003-1991-5174","position":6,"is_corresponding":false},{"id":430452,"name":"Audra A. Hargett","orcid":"0000-0002-0459-1392","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:00:34.490087Z","pmid":"38330012","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":[]}