{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:06:29Z","timestamp":1791932789892,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology (DST), Science and Engineering Research Board","award":["CRG\/2018\/000129"],"award-info":[{"award-number":["CRG\/2018\/000129"]}]},{"name":"Department of Science and Technology (DST), Science and Engineering Research Board","award":["IMURA 0716"],"award-info":[{"award-number":["IMURA 0716"]}]},{"name":"Department of Science and Technology (DST), Science and Engineering Research Board","award":["APP1002486"],"award-info":[{"award-number":["APP1002486"]}]},{"name":"Department of Science and Technology (DST), Science and Engineering Research Board","award":["APP1103050"],"award-info":[{"award-number":["APP1103050"]}]},{"name":"Department of Biotechnology, India","award":["CRG\/2018\/000129"],"award-info":[{"award-number":["CRG\/2018\/000129"]}]},{"name":"Department of Biotechnology, India","award":["IMURA 0716"],"award-info":[{"award-number":["IMURA 0716"]}]},{"name":"Department of Biotechnology, India","award":["APP1002486"],"award-info":[{"award-number":["APP1002486"]}]},{"name":"Department of Biotechnology, India","award":["APP1103050"],"award-info":[{"award-number":["APP1103050"]}]},{"name":"National Health and Medical Research Council of Australia","award":["CRG\/2018\/000129"],"award-info":[{"award-number":["CRG\/2018\/000129"]}]},{"name":"National Health and Medical Research Council of Australia","award":["IMURA 0716"],"award-info":[{"award-number":["IMURA 0716"]}]},{"name":"National Health and Medical Research Council of Australia","award":["APP1002486"],"award-info":[{"award-number":["APP1002486"]}]},{"name":"National Health and Medical Research Council of Australia","award":["APP1103050"],"award-info":[{"award-number":["APP1103050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Signal-dependent transport into and out of the nucleus mediated by members of the importin (IMP) superfamily of nuclear transporters is critical to the eukaryotic function and a point of therapeutic intervention with the potential to limit disease progression and pathogenic outcomes. Although the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii both retain unique IMP\u03b1 genes that are essential, a detailed analysis of their properties has not been performed. As a first step to validate apicomplexan IMP\u03b1 as a target, we set out to compare the properties of P. falciparum and T. gondii IMP\u03b1 (PfIMP\u03b1 and TgIMP\u03b1, respectively) to those of mammalian IMP\u03b1, as exemplified by Mus musculus IMP\u03b1 (MmIMP\u03b1). Close similarities were evident, with all three showing high-affinity binding to modular nuclear localisation signals (NLSs) from apicomplexans as well as Simian virus SV40 large tumour antigen (T-ag). PfIMP\u03b1 and TgIMP\u03b1 were also capable of binding to mammalian IMP\u03b21 (MmIMP\u03b21) with high affinity; strikingly, NLS binding by PfIMP\u03b1 and TgIMP\u03b1 could be inhibited by the mammalian IMP\u03b1 targeting small molecules ivermectin and GW5074 through direct binding to PfIMP\u03b1 and TgIMP\u03b1 to perturb the \u03b1-helical structure. Importantly, GW5074 could be shown for the first time to resemble ivermectin in being able to limit growth of P. falciparum. The results confirm apicomplexan IMP\u03b1 as a viable target for the development of therapeutics, with agents targeting it worthy of further consideration as an antimalarial.<\/jats:p>","DOI":"10.3390\/ijms232213899","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:26:37Z","timestamp":1668392797000},"page":"13899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Conservation of Importin \u03b1 Function in Apicomplexans: Ivermectin and GW5074 Target Plasmodium falciparum Importin \u03b1 and Inhibit Parasite Growth in Culture"],"prefix":"10.3390","volume":"23","author":[{"given":"Sujata B.","family":"Walunj","sequence":"first","affiliation":[{"name":"Molecular Parasitology Lab., Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India"},{"name":"Nuclear Signalling Lab., Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Monash, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Nuclear Signalling Lab., Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Monash, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie M.","family":"Wagstaff","sequence":"additional","affiliation":[{"name":"Nuclear Signalling Lab., Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Monash, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Patankar","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Lab., Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-4745","authenticated-orcid":false,"given":"David A.","family":"Jans","sequence":"additional","affiliation":[{"name":"Nuclear Signalling Lab., Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Monash, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12688\/f1000research.7924.1","article-title":"Recent Advances in Understanding Apicomplexan Parasites","volume":"5","author":"Seeber","year":"2016","journal-title":"F1000Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cell.2016.07.055","article-title":"Malaria: Biology and Disease","volume":"167","author":"Cowman","year":"2016","journal-title":"Cell"},{"key":"ref_3","unstructured":"(2021). 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