{"doi":"10.64898/2026.01.14.699498","title":"Dynamic hinge-motion of PfRIPR revealed by malaria invasion inhibitory antibodies","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  The PfPCRCR complex is essential for invasion of human erythrocytes by the deadliest malaria parasite,\n                  <jats:italic>Plasmodium falciparum</jats:italic>\n                  . Antibodies against each subunit of PfPCRCR prevent erythrocyte invasion and the PfRH5 component is currently the most advanced blood-stage malaria vaccine. Central within PfPCRCR is PfRIPR. This complex molecule contains a core and a flexible tail and allows PfPCRCR to bridge the parasite and erythrocyte during invasion. In this study, we generated a small panel of human monoclonal antibodies against PfRIPR. We structurally characterised four PfRIPR tail-binding antibodies in complex with PfRIPR fragments. We show that growth-inhibitory antibody RP.012 induces a kink in the PfRIPR tail while non-inhibitory antibodies do not. Furthermore, we show that these four antibodies modulate each other, either through antagonism or by acting synergistically. These studies have implications for the design of PfRIPR-based vaccine immunogens and indicate that the tail of PfRIPR undergoes essential conformational changes during erythrocyte invasion.\n                </jats:p>","journal":null,"year":null,"id":633249,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1641724,"name":"Andrew J.R. Cooper","orcid":null,"position":1,"is_corresponding":false},{"id":1641725,"name":"Egle Butkeviciute","orcid":null,"position":2,"is_corresponding":false},{"id":1641726,"name":"Lawrence T. Wang","orcid":null,"position":3,"is_corresponding":false},{"id":1641727,"name":"Emily Egerton-Warburton","orcid":null,"position":4,"is_corresponding":false},{"id":564433,"name":"Joshua Tan","orcid":"0000-0002-6661-6372","position":5,"is_corresponding":false},{"id":471468,"name":"Matthew K. Higgins","orcid":"0000-0002-2870-1955","position":6,"is_corresponding":false},{"id":1170030,"name":"Brendan Farrell","orcid":"0000-0001-9919-9141","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Dynamic hinge-motion of PfRIPR revealed by malaria invasion inhibitory antibodies","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  The PfPCRCR complex is essential for invasion of human erythrocytes by the deadliest malaria parasite,\n                  <jats:italic>Plasmodium falciparum</jats:italic>\n                  . Antibodies against each subunit of PfPCRCR prevent erythrocyte invasion and the PfRH5 component is currently the most advanced blood-stage malaria vaccine. Central within PfPCRCR is PfRIPR. This complex molecule contains a core and a flexible tail and allows PfPCRCR to bridge the parasite and erythrocyte during invasion. In this study, we generated a small panel of human monoclonal antibodies against PfRIPR. We structurally characterised four PfRIPR tail-binding antibodies in complex with PfRIPR fragments. We show that growth-inhibitory antibody RP.012 induces a kink in the PfRIPR tail while non-inhibitory antibodies do not. Furthermore, we show that these four antibodies modulate each other, either through antagonism or by acting synergistically. These studies have implications for the design of PfRIPR-based vaccine immunogens and indicate that the tail of PfRIPR undergoes essential conformational changes during erythrocyte invasion.\n                </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":null,"pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"","grant_id":"220797/Z/20/Z","title":null},{"funder_name":"Medical Research Council","grant_id":"MR/Z505687/1","title":null},{"funder_name":"Gates Foundation","grant_id":"INV-078815","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.64898/2026.01.14.699498","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.64898/2026.01.14.699498","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T11:35:16.006885Z","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":[]}