{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:51:21Z","timestamp":1790628681638,"version":"4.1.0"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"UKRI | Medical Research Council","award":["MR\/R008485\/1"],"award-info":[{"award-number":["MR\/R008485\/1"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,1,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Malaria parasites alter multiple properties of the host erythrocyte by exporting proteins into the host cell. Many exported proteins contain a five-amino acid motif called the\n            <jats:italic>Plasmodium<\/jats:italic>\n            export element (PEXEL) that is cleaved by the parasite protease Plasmepsin V (PM V). The presence of a PEXEL is considered a signature of protein export and has been used to identify a large number of exported proteins. The export of proteins becomes essential midway through the intraerythrocytic cycle\u2014preventing protein export blocks parasite development 18\u201324 h after invasion. However, a genetic investigation revealed that the absence of the PEXEL protein PFA0210c (PF3D7_0104200) causes parasite development to arrest immediately after invasion. We now show that this protein is cleaved by PM V but not exported into the host erythrocyte and instead functions in the parasitophorous vacuole; hence, the protein was renamed PV6. We additionally show that the lysine residue that becomes the N-terminus of PV6 after processing by PM V prevents export. This is the first example of a native\n            <jats:italic>Plasmodium falciparum<\/jats:italic>\n            PM V substrate that remains in the parasitophorous vacuole. We also provide evidence suggesting that the parasite may produce at least one additional essential, non-exported PM V substrate. Therefore, the presence of a PEXEL and, hence, processing of a protein by PM V do not always target a protein for export, and PM V likely has a broader function in parasite growth beyond processing exported proteins. Furthermore, we utilized this finding to investigate possible requirements for protein export further.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>In the manuscript, the authors investigate the role of the protease Plasmepsin V in the parasite\u2013host interaction. Whereas processing by Plasmepsin V was previously thought to target a protein for export into the host cell, the authors now show that there are proteins cleaved by this protease that are not exported but instead function at the host\u2013parasite interface. This changes the view of this protease, which turns out to have a much broader role than anticipated. The result shows that the protease may have a function much more similar to that of related organisms. The authors also investigate the requirements for protein export by analyzing exported and non-exported proteins and find commonalities between the proteins of each set that further our understanding of the requirements for protein export.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01223-23","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T14:03:46Z","timestamp":1702303426000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Identification of a non-exported Plasmepsin V substrate that functions in the parasitophorous vacuole of malaria parasites"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6099-6183","authenticated-orcid":false,"given":"Aline","family":"Fr\u00e9ville","sequence":"first","affiliation":[{"name":"Department of Infection Biology, London School of Hygiene &amp; Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida","family":"Ressurrei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, London School of Hygiene &amp; Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6099-6183","authenticated-orcid":false,"given":"Christiaan","family":"van 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MA Muheljic A Sha J Wohlschlegel JA Beck JR. 2023. 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