{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T15:50:36Z","timestamp":1782143436379,"version":"3.54.5"},"reference-count":61,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001215","name":"La Trobe University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001215","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DE200100367"],"award-info":[{"award-number":["DE200100367"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Adenoviral pVII proteins are multifunctional, highly basic, histone\u2010like proteins that can bind to and transport the viral genome into the host cell nucleus. Despite the identification of several nuclear localization signals (NLSs) in the pVII protein of human adenovirus (HAdV)2, the mechanistic details of nuclear transport are largely unknown. Here we provide a full characterization of the nuclear import of precursor (Pre\u2010) pVII protein from an ancient siadenovirus, frog siadenovirus 1 (FrAdV1), using a combination of structural, functional, and biochemical approaches. Two strong NLSs (termed NLSa and NLSd) interact with importin (IMP)\u03b21 and IMP\u03b1, respectively, and are the main drivers of nuclear import. A weaker NLS (termed NLSb) also contributes, together with an additional signal (NLSc) which we found to be important for nucleolar targeting and intranuclear binding. Expression of wild\u2010type and NLS defective derivatives Pre\u2010pVII in the presence of selective inhibitors of different nuclear import pathways revealed that, unlike its human counterpart, FrAdV1 Pre\u2010pVII nuclear import is dependent on IMP\u03b1\/\u03b21 and IMP\u03b21, but not on transportin\u20101 (IMP\u03b22). Clearly, AdVs evolved to maximize the nuclear import pathways for the pVII proteins, whose subcellular localization is the result of a complex process. Therefore, our results pave the way for an evolutionary comparison of the interaction of different AdVs with the host cell nuclear transport machinery.<\/jats:p>","DOI":"10.1111\/tra.12953","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T04:59:32Z","timestamp":1726808372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mechanistic Insights Into an Ancient Adenovirus Precursor Protein\n                    <scp>VII<\/scp>\n                    Show Multiple Nuclear Import Receptor Pathways"],"prefix":"10.1111","volume":"25","author":[{"given":"Sepehr","family":"Nematollahzadeh","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajani","family":"Athukorala","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Anatomy, Physiology, and Pharmacology, School of Agriculture, Biomedicine and Environment La Trobe University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla\u00a0M.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"School of Dentistry and Medical Sciences Biomedical Sciences Charles Sturt University  Wagga Wagga New South Wales Australia"},{"name":"Gulbali Institute Charles Sturt University  Wagga Wagga New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pavan","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Atelie\u2010Djossou","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Padua  Padua 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