{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:23:27Z","timestamp":1792531407200,"version":"4.5.0"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"51","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,12,20]]},"abstract":"<jats:p>\n            Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria,\n            <jats:italic>Plasmodium falciparum<\/jats:italic>\n            , has developed resistance to nearly all currently available antimalarial drugs. The\n            <jats:italic>P. falciparum<\/jats:italic>\n            Niemann-Pick type C1\u2013related (PfNCR1) transporter has been identified as a druggable target, but its structure and detailed molecular mechanism are not yet available. Here, we present three structures of PfNCR1 with and without the functional inhibitor MMV009108 at resolutions between 2.98 and 3.81 \u00c5 using single-particle cryo\u2013electron microscopy (cryo-EM), suggesting that PfNCR1 binds cholesterol and forms a cholesterol transport tunnel to modulate the composition of the parasite plasma membrane. Cholesterol efflux assays show that PfNCR1 is an exporter capable of extruding cholesterol from the membrane. Additionally, the inhibition mechanism of MMV009108 appears to be due to a direct blockage of PfNCR1, preventing this transporter from shuttling cholesterol.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adq6651","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T18:58:47Z","timestamp":1734548327000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["The\n            <i>Plasmodium falciparum<\/i>\n            NCR1 transporter is an antimalarial target that exports cholesterol from the parasite\u2019s plasma membrane"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0135-4970","authenticated-orcid":true,"given":"Zhemin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5795-0232","authenticated-orcid":true,"given":"Meinan","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-1046","authenticated-orcid":true,"given":"Xu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepalika","family":"Bandara","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3895-135X","authenticated-orcid":true,"given":"Meng","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Northeastern University School of Pharmacy, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8666-3248","authenticated-orcid":true,"given":"Eva S.","family":"Istvan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA."},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2335-2642","authenticated-orcid":true,"given":"Xinran","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3800-2365","authenticated-orcid":true,"given":"Marios L.","family":"Tringides","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7722-614X","authenticated-orcid":true,"given":"William D.","family":"Gregor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4325-1216","authenticated-orcid":true,"given":"Masaru","family":"Miyagi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3033-2212","authenticated-orcid":true,"given":"Jenna","family":"Oberstaller","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases, Department of Global Health, University of South Florida, 3720 Spectrum Boulevard, Suite 404, Tampa, FL 33612, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3707-7979","authenticated-orcid":true,"given":"John H.","family":"Adams","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases, Department of Global Health, University of South Florida, 3720 Spectrum Boulevard, Suite 404, Tampa, FL 33612, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-7922","authenticated-orcid":true,"given":"Youwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2602-023X","authenticated-orcid":true,"given":"Marvin T.","family":"Nieman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-2143","authenticated-orcid":true,"given":"Johannes","family":"von Lintig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3529-8399","authenticated-orcid":true,"given":"Daniel E.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA."},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-1227","authenticated-orcid":true,"given":"Edward W.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"WHO. 2022. World Malaria Report 2022. World Health Organization Geneva Switzerland."},{"key":"e_1_3_2_3_2","unstructured":"CDC. 2018. Drug Resistance in the Malaria-Endemic World. 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