{"doi":"10.1093/infdis/jiab550","title":"An Invariant Protein That Colocalizes With VAR2CSA on <i>Plasmodium falciparum</i>-Infected Red Cells Binds to Chondroitin Sulfate A","abstract":"BACKGROUND: Plasmodium falciparum-infected red blood cells (iRBCs) bind and sequester in deep vascular beds, causing malaria-related disease and death. In pregnant women, VAR2CSA binds to chondroitin sulfate A (CSA) and mediates placental sequestration, making it the major placental malaria (PM) vaccine target. METHODS: In this study, we characterize an invariant protein associated with PM called P falciparum chondroitin sulfate A ligand (PfCSA-L). RESULTS: Recombinant PfCSA-L binds both placental CSA and VAR2CSA with nanomolar affinity, and it is coexpressed on the iRBC surface with VAR2CSA. Unlike VAR2CSA, which is anchored by a transmembrane domain, PfCSA-L is peripherally associated with the outer surface of knobs through high-affinity protein-protein interactions with VAR2CSA. This suggests that iRBC sequestration involves complexes of invariant and variant surface proteins, allowing parasites to maintain both diversity and function at the iRBC surface. CONCLUSIONS: The PfCSA-L is a promising target for intervention because it is well conserved, exposed on infected cells, and expressed and localized with VAR2CSA.","journal":"The Journal of Infectious Diseases","year":2021,"id":195824,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9647,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":569230,"name":"Bethany J. Jenkins","orcid":null,"position":1,"is_corresponding":false},{"id":768439,"name":"Harold Obiakor","orcid":null,"position":2,"is_corresponding":false},{"id":768440,"name":"Daniel Shaji","orcid":null,"position":3,"is_corresponding":false},{"id":285302,"name":"Atis Muehlenbachs","orcid":"0000-0003-1117-7357","position":4,"is_corresponding":false},{"id":767760,"name":"Jean‐Philippe Semblat","orcid":"0000-0001-9321-5008","position":5,"is_corresponding":false},{"id":767761,"name":"Benoît Gamain","orcid":"0000-0002-8255-2145","position":6,"is_corresponding":false},{"id":414017,"name":"Justin Doritchamou","orcid":"0000-0002-4589-7216","position":7,"is_corresponding":false},{"id":457372,"name":"Sanjay A. Desai","orcid":"0000-0003-2150-2483","position":8,"is_corresponding":false},{"id":299008,"name":"Nicholas J. MacDonald","orcid":"0000-0002-8162-4514","position":9,"is_corresponding":false},{"id":299010,"name":"David L. Narum","orcid":"0000-0003-3041-5402","position":10,"is_corresponding":false},{"id":414999,"name":"Robert Morrison","orcid":null,"position":11,"is_corresponding":false},{"id":768441,"name":"Tracy Saveria","orcid":null,"position":12,"is_corresponding":false},{"id":414018,"name":"Marissa Vignali","orcid":"0000-0002-7319-3371","position":13,"is_corresponding":false},{"id":285299,"name":"Andrew V. Oleinikov","orcid":"0009-0009-9386-1208","position":14,"is_corresponding":false},{"id":285307,"name":"Michal Fried","orcid":"0000-0002-5478-6526","position":15,"is_corresponding":false},{"id":236042,"name":"Patrick E. Duffy","orcid":"0000-0002-4483-5005","position":16,"is_corresponding":false},{"id":686365,"name":"Gladys J. Keitany","orcid":"0000-0002-3611-1066","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:50:11.609550Z","pmid":"34718641","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":[]}