{"doi":"10.1101/2023.10.26.564164","title":"A <i>Toxoplasma gondii</i> O-glycosyltransferase that modulates bradyzoite cyst wall rigidity is structurally and functionally distinct from host homologues","abstract":"Abstract Infection with the Apicomplexan protozoan Toxoplasma gondii can be life-threatening in immunocompromised hosts. Transmission frequently occurs through the oral ingestion of T. gondii bradyzoite cysts, which transition to tachyzoites, disseminate, and then form cysts containing bradyzoites in the central nervous system, resulting in latent infection. There are currently no effective treatments to cure latent infection. Bradyzoites are encapsulated by a cyst wall that is critical for immune evasion, survival, and transmission. Cyst wall rigidity is influenced by the O-glycosylation of the mucin domain of the cyst wall protein CST1 by mucin-type O-glycosyltransferases (GalNAc-Ts). Here, we report the first structures of a protozoan GalNAc-T, T.gondii -GalNAc-T3 in the apo state and in complex with glycopeptide substrates. The structures reveal features that are strictly conserved in Apicomplexan homologues of T.gondii -GalNAc-T3, including a unique 2 nd metal binding site that is coupled to substrate binding and enzymatic activity in vitro and cyst wall O-glycosylation in T. gondii . Additional structural features illustrate the divergence of GalNAc-Ts from parasite to host and highlight multiple druggable sites in T.gondii -GalNAc-T3 and its homologues in Apicomplexa that are responsible for a wide range of parasitic diseases.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":413234,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320658,"name":"Tadakimi Tomita","orcid":"0000-0001-8809-3333","position":1,"is_corresponding":false},{"id":305014,"name":"Thomas Gerken","orcid":"0000-0002-7919-7613","position":2,"is_corresponding":false},{"id":1077008,"name":"Collin J. Ballard","orcid":"0000-0003-2869-6970","position":3,"is_corresponding":false},{"id":439443,"name":"Yong Sok Lee","orcid":"0000-0002-6222-1197","position":4,"is_corresponding":false},{"id":320665,"name":"Louis M. Weiss","orcid":"0000-0002-0357-7396","position":5,"is_corresponding":false},{"id":432038,"name":"N.L. Samara","orcid":"0000-0001-7152-2939","position":6,"is_corresponding":false},{"id":1194670,"name":"Pranav Kumar","orcid":"0000-0002-4659-7725","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T01:21:57.641539Z","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":[]}