{"doi":"10.1073/pnas.2104166118","title":"Complement C1s cleaves PfEMP1 at interdomain conserved sites inhibiting <i>Plasmodium falciparum</i> cytoadherence","abstract":"Significance Mature asexual stages of Plasmodium falciparum -infected erythrocytes (IEs) bind to endothelium to avoid splenic clearance. The PfEMP1 family is the major cytoadhesion ligand at the IE surface and is essential for parasite sequestration. In this study, we show that complement component 1s (C1s), found in serum, cleaves PfEMP1 on the IEs to prevent binding to endothelial cells. We find that the C1s cleavage sites are maintained at semiconserved arginine motifs located at interdomain regions between PfEMP1 receptor-binding domains and upstream of the transmembrane region. This suggests that parasites have taken advantage of a human serum protease, either to escape antibody recognition of sequestered parasites or to dampen sequestration and pathogenesis from uncontrolled inflammatory responses threatening host survival.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":180341,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"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":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":729005,"name":"Leanne M. Low","orcid":"0000-0002-1976-3767","position":1,"is_corresponding":false},{"id":729006,"name":"Ashley N. Just","orcid":"0000-0002-7993-9867","position":2,"is_corresponding":false},{"id":729007,"name":"Sai Sundar Rajan Raghavan","orcid":"0000-0002-2575-2685","position":3,"is_corresponding":false},{"id":729008,"name":"Christian W. Wang","orcid":"0000-0003-3140-6989","position":4,"is_corresponding":false},{"id":363404,"name":"Paola Carolina Valenzuela Leon","orcid":"0000-0002-5740-5178","position":5,"is_corresponding":false},{"id":729009,"name":"J. Alexandra Rowe","orcid":"0000-0002-7702-1892","position":6,"is_corresponding":false},{"id":281118,"name":"Joseph D. Smith","orcid":"0000-0002-7915-6360","position":7,"is_corresponding":false},{"id":260442,"name":"Thomas Lavstsen","orcid":"0000-0002-3044-4249","position":8,"is_corresponding":false},{"id":260436,"name":"Louise Turner","orcid":"0000-0003-4494-2289","position":9,"is_corresponding":false},{"id":294696,"name":"Eric Calvo","orcid":"0000-0001-7880-2730","position":10,"is_corresponding":false},{"id":439633,"name":"Louis H. Miller","orcid":"0000-0003-3420-1284","position":11,"is_corresponding":false},{"id":467980,"name":"Yvonne Azasi","orcid":"0000-0002-4993-8046","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:53.089578Z","pmid":"34035177","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":[]}