{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:45:49Z","timestamp":1791895549015,"version":"4.3.4"},"reference-count":39,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["20797\/Z\/20\/Z"],"award-info":[{"award-number":["20797\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 746"],"award-info":[{"award-number":["SFB 746"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["TP 20"],"award-info":[{"award-number":["TP 20"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,10,4]]},"abstract":"<jats:p>\n                    Basigin is an essential host receptor for invasion of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    into human erythrocytes, interacting with parasite surface protein PfRH5. PfRH5 is a leading blood-stage malaria vaccine candidate and a target of growth-inhibitory antibodies. Here, we show that erythrocyte basigin is exclusively found in one of two macromolecular complexes, bound either to plasma membrane Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -ATPase 1\/4 (PMCA1\/4) or to monocarboxylate transporter 1 (MCT1). PfRH5 binds to each of these complexes with a higher affinity than to isolated basigin ectodomain, making it likely that these are the physiological targets of PfRH5. PMCA-mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    export is not affected by PfRH5, making it unlikely that this is the mechanism underlying changes in calcium flux at the interface between an erythrocyte and the invading parasite. However, our studies rationalise the function of the most effective growth-inhibitory antibodies targeting PfRH5. While these antibodies do not reduce the binding of PfRH5 to monomeric basigin, they do reduce its binding to basigin-PMCA and basigin-MCT complexes. This indicates that the most effective PfRH5-targeting antibodies inhibit growth by sterically blocking the essential interaction of PfRH5 with basigin in its physiological context.\n                  <\/jats:p>","DOI":"10.7554\/elife.83681","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T12:20:08Z","timestamp":1696508408000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.83681","source":"Crossref","is-referenced-by-count":22,"title":["Erythrocyte invasion-neutralising antibodies prevent Plasmodium falciparum RH5 from binding to basigin-containing membrane protein complexes"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6842-6056","authenticated-orcid":true,"given":"Abhishek","family":"Jamwal","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Oxford","place":["Oxford, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina F","family":"Constantin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0245cg223","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Physiology, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Hirschi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Oxford","place":["Oxford, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Henrich","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0245cg223","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Physiology, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Bildl","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0245cg223","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Physiology, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Fakler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0245cg223","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Physiology, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]},{"name":"Signalling Research Centres BIOSS and CIBS","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9415-1357","authenticated-orcid":true,"given":"Simon J","family":"Draper","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Oxford","place":["Oxford, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3557-0591","authenticated-orcid":true,"given":"Uwe","family":"Schulte","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0245cg223","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Physiology, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]},{"name":"Signalling Research Centres BIOSS and CIBS","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2870-1955","authenticated-orcid":true,"given":"Matthew K","family":"Higgins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Oxford","place":["Oxford, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,10,5]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.cell.2019.05.025","article-title":"Human antibodies that slow erythrocyte invasion potentiate malaria-neutralizing antibodies","volume":"178","author":"Alanine","year":"2019","journal-title":"Cell"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1093\/infdis\/jit070","article-title":"An ATP2B4 polymorphism protects against malaria in pregnancy","volume":"207","author":"Bedu-Addo","year":"2013","journal-title":"The Journal of Infectious Diseases"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.007955","article-title":"Extending the dynamic range of label-free mass spectrometric quantification of affinity purifications","volume":"11","author":"Bildl","year":"2012","journal-title":"Molecular & Cellular Proteomics"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1073\/pnas.1616903114","article-title":"One-step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen","volume":"114","author":"Campeotto","year":"2017","journal-title":"PNAS"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.chom.2017.07.003","article-title":"The molecular basis of erythrocyte invasion by malaria parasites","volume":"22","author":"Cowman","year":"2017","journal-title":"Cell Host & Microbe"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1038\/nature10606","article-title":"Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum","volume":"480","author":"Crosnier","year":"2011","journal-title":"Nature"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"245","DOI":"10.4049\/jimmunol.1302045","article-title":"Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5","volume":"192","author":"Douglas","year":"2014","journal-title":"Journal of Immunology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.chom.2014.11.017","article-title":"A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys","volume":"17","author":"Douglas","year":"2015","journal-title":"Cell Host & Microbe"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09894-4","article-title":"A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates","volume":"10","author":"Douglas","year":"2019","journal-title":"Nature Communications"},{"key":"bib10","doi-asserted-by":"publisher","DOI":"10.1101\/2023.01.30.526221","article-title":"Structure of the PfRCR Complex Which Bridges the Malaria Parasite and Erythrocyte during Invasion","volume-title":"bioRxiv","author":"Farrell","year":"2023"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1124\/pr.119.018762","article-title":"Monocarboxylate transporters (SLC16): function, regulation, and role in health and disease","volume":"72","author":"Felmlee","year":"2020","journal-title":"Pharmacological Reviews"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06075-7","article-title":"Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin","volume":"9","author":"Gong","year":"2018","journal-title":"Nature Communications"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1113\/jphysiol.2002.035899","article-title":"Human skeletal muscle and erythrocyte proteins involved in acid-base homeostasis: adaptations to chronic hypoxia","volume":"548","author":"Juel","year":"2003","journal-title":"The Journal of Physiology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"3896","DOI":"10.1093\/emboj\/19.15.3896","article-title":"CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression","volume":"19","author":"Kirk","year":"2000","journal-title":"The EMBO Journal"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/imr.12802","article-title":"Complement in malaria immunity and vaccines","volume":"293","author":"Kurtovic","year":"2020","journal-title":"Immunological Reviews"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"205","DOI":"10.4269\/ajtmh.1993.48.205","article-title":"Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia","volume":"48","author":"Makler","year":"1993","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00125","article-title":"Lactate transport and receptor actions in cerebral malaria","volume":"8","author":"Mariga","year":"2014","journal-title":"Frontiers in Neuroscience"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.medj.2021.03.014","article-title":"Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination","volume":"2","author":"Minassian","year":"2021","journal-title":"Med"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1074\/mcp.M115.054080","article-title":"Cryo-slicing Blue Native-Mass Spectrometry (csBN-MS), a Novel Technology for High Resolution Complexome Profiling","volume":"15","author":"M\u00fcller","year":"2016","journal-title":"Molecular & Cellular Proteomics"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1093\/jb\/mvv127","article-title":"Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners","volume":"159","author":"Muramatsu","year":"2016","journal-title":"Journal of Biochemistry"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.96381","article-title":"Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions","volume":"2","author":"Payne","year":"2017","journal-title":"JCI Insight"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28601-4","article-title":"Heterotypic interactions drive antibody synergy against a malaria vaccine candidate","volume":"13","author":"Ragotte","year":"2022","journal-title":"Nature Communications"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0596-y","article-title":"Quantitative comparative analysis of human erythrocyte surface proteins between individuals from two genetically distinct populations","volume":"2","author":"Ravenhill","year":"2019","journal-title":"Communications Biology"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1073\/pnas.1415466112","article-title":"Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion","volume":"112","author":"Reddy","year":"2015","journal-title":"PNAS"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1186\/s40101-020-00251-9","article-title":"Plasmodium-a brief introduction to the parasites causing human malaria and their basic biology","volume":"40","author":"Sato","year":"2021","journal-title":"Journal of Physiological Anthropology"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1038\/s41564-022-01261-2","article-title":"PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum","volume":"7","author":"Scally","year":"2022","journal-title":"Nature Microbiology"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1093\/emboj\/19.8.1777","article-title":"Supercomplexes in the respiratory chains of yeast and mammalian mitochondria","volume":"19","author":"Sch\u00e4gger","year":"2000","journal-title":"The EMBO Journal"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.neuron.2017.09.038","article-title":"Neuroplastin and Basigin Are Essential Auxiliary Subunits of Plasma Membrane Ca2+-ATPases and Key Regulators of Ca2+ Clearance","volume":"96","author":"Schmidt","year":"2017","journal-title":"Neuron"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1152\/physrev.00028.2016","article-title":"The Plasma Membrane Calcium ATPases and Their Role as Major New Players in Human Disease","volume":"97","author":"Stafford","year":"2017","journal-title":"Physiological Reviews"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.4049\/jimmunol.1501889","article-title":"Association of CD147 and Calcium Exporter PMCA4 Uncouples IL-2 Expression from Early TCR Signaling","volume":"196","author":"Supper","year":"2016","journal-title":"Journal of Immunology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.pt.2016.07.003","article-title":"Functional antibodies and protection against blood-stage malaria","volume":"32","author":"Teo","year":"2016","journal-title":"Trends in Parasitology"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/nature11334","article-title":"Genome-wide association study indicates two novel resistance loci for severe malaria","volume":"489","author":"Timmann","year":"2012","journal-title":"Nature"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/s41579-019-0306-2","article-title":"Plasmodium asexual growth and sexual development in the haematopoietic niche of the host","volume":"18","author":"Venugopal","year":"2020","journal-title":"Nature Reviews. Microbiology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.chom.2016.06.004","article-title":"Essential Role of the PfRh5\/PfRipr\/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes","volume":"20","author":"Volz","year":"2016","journal-title":"Cell Host & Microbe"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.cell.2020.11.043","article-title":"Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates","volume":"184","author":"Wang","year":"2021","journal-title":"Cell"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004670","article-title":"Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes","volume":"11","author":"Weiss","year":"2015","journal-title":"PLOS Pathogens"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41586-018-0779-6","article-title":"Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex","volume":"565","author":"Wong","year":"2019","journal-title":"Nature"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/nature13715","article-title":"Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies","volume":"515","author":"Wright","year":"2014","journal-title":"Nature"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1084\/jem.20150032","article-title":"Basigin is a druggable target for host-oriented antimalarial interventions","volume":"212","author":"Zenonos","year":"2015","journal-title":"The Journal of Experimental Medicine"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/83681\/elife-83681-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/83681\/elife-83681-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/83681","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T10:30:44Z","timestamp":1697106644000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/83681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,5]]},"references-count":39,"alternative-id":["10.7554\/eLife.83681"],"URL":"https:\/\/doi.org\/10.7554\/elife.83681","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.09.23.509221","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.09.23.509221","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.83681.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.83681.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.83681.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,5]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e83681"}}