{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:21:29Z","timestamp":1760955689123,"version":"3.37.3"},"reference-count":73,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T00:00:00Z","timestamp":1488153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001164","name":"Australian Synchrotron","doi-asserted-by":"publisher","award":["CAP8221"],"award-info":[{"award-number":["CAP8221"]}],"id":[{"id":"10.13039\/501100001164","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>The fungal pathogen <jats:italic>Aspergillus fumigatus<\/jats:italic> has been implicated in a drastic increase in life\u2010threatening infections over the past decade. However, compared to other microbial pathogens, little is known about the essential molecular processes of this organism. One such fundamental process is <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> replication. The protein responsible for ensuring processive <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> replication is <jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> (proliferating cell nuclear antigen, also known as the sliding clamp), which clamps the replicative polymerase to <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>. Here we present the first crystal structure of a sliding clamp from a pathogenic fungus (<jats:italic>A. fumigatus<\/jats:italic>), at 2.6\u00c5. Surprisingly, the structure bears more similarity to the human sliding clamp than other available fungal sliding clamps. Reflecting this, fluorescence polarization experiments demonstrated that Afum<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> interacts with the <jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content>\u2010interacting protein (<jats:styled-content style=\"fixed-case\">PIP<\/jats:styled-content>\u2010box) motif of human p21 with an affinity (<jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub>) of 3.1 \u03bc<jats:sc>m<\/jats:sc>. Molecular dynamics simulations were carried out to better understand how Afum<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> interacts with human p21. These simulations revealed that the <jats:styled-content style=\"fixed-case\">PIP<\/jats:styled-content>\u2010box bound to Afu<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> forms a secondary structure similar to that observed in the human complex, with a central 3<jats:sub>10<\/jats:sub> helix contacting the hydrophobic surface pocket of Afum<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> as well as a \u03b2\u2010strand that forms an antiparallel sheet with the Afum<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> surface. Differences in the 3<jats:sub>10<\/jats:sub> helix interaction with <jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content>, attributed to residue Thr131 of Afum<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content>, and a less stable \u03b2\u2010strand formation, attributed to residues Gln123 and His125 of Afum<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content>, are likely causes of the over 10\u2010fold lower affinity of the p21 <jats:styled-content style=\"fixed-case\">PIP<\/jats:styled-content>\u2010box for Afum<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> as compared to <jats:styled-content style=\"fixed-case\">hPCNA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Database<\/jats:title><jats:p>The atomic coordinates and structure factors for the <jats:italic>Aspergillus fumigatus<\/jats:italic> sliding clamp can be found in the <jats:styled-content style=\"fixed-case\">RCSB<\/jats:styled-content> Protein Data Bank (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.rcsb.org\">http:\/\/www.rcsb.org<\/jats:ext-link>) under the accession code <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.rcsb.org\/pdb\/search\/structidSearch.do?structureId=5TUP\">5TUP<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/febs.14035","type":"journal-article","created":{"date-parts":[[2017,2,6]],"date-time":"2017-02-06T14:57:23Z","timestamp":1486393043000},"page":"985-1002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Structure of the sliding clamp from the fungal pathogen <i>Aspergillus fumigatus<\/i> (Afum<scp>PCNA<\/scp>) and interactions with Human p21"],"prefix":"10.1111","volume":"284","author":[{"given":"Andrew C.","family":"Marshall","sequence":"first","affiliation":[{"name":"School 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