{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:52:51Z","timestamp":1786978371812,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1193524N"],"award-info":[{"award-number":["1193524N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","award":["FAF\u2010F\/2018\/1208"],"award-info":[{"award-number":["FAF\u2010F\/2018\/1208"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004727","name":"Vlaams Instituut voor Biotechnologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004727","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The Alternative Lengthening of Telomeres (ALT) mechanism enables telomere maintenance, contributing to the immortality of certain cancer cells. Disrupting the interaction between testis\u2010specific Y\u2010encoded\u2010like protein 5 (TSPYL5) and ubiquitin\u2010specific protease 7 (USP7) has emerged as a promising strategy to target ALT\u2010dependent cancers. While the N\u2010terminal MATH domain of USP7 mediates the protein interaction, the regions of TSPYL5 involved in binding remain unclear. Here, we present a structural analysis of the TSPYL5\u2013USP7 interaction to guide targeted therapeutic strategies. We showed that TSPYL5 is intrinsically disordered, with an unfolded N\u2010terminal region and partial structure in the C\u2010terminal half.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , recombinantly expressed TSPYL5 binds USP7 with nanomolar affinity and is prone to C\u2010terminal truncation. However, the truncated form retained a similar binding affinity for USP7, suggesting the primary interaction site resides in the N\u2010terminal region of TSPYL5. We identified three key binding hotspots within TSPYL5: residues 65\u201397, residues 210\u2013262, and residues 368\u2013388. Moreover, TSPYL5 forms trimers that further assemble into hexamers. This study provides the first structural and quantitative analysis of the TSPYL5\u2013USP7 interaction, highlighting these three binding sites. These findings lay the groundwork for the development of novel inhibitors targeting ALT\u2010dependent cancers.\n                  <\/jats:p>","DOI":"10.1002\/pro.70116","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T08:14:40Z","timestamp":1745309680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Structural insights into the interaction between testis\u2010specific Y\u2010encoded\u2010like protein 5 and ubiquitin\u2010specific protease 7"],"prefix":"10.1002","volume":"34","author":[{"given":"Marine","family":"Ancia","sequence":"first","affiliation":[{"name":"Medicinal Chemistry Research Group, Louvain Drug Research Institute Universit\u00e9 catholique de Louvain  Brussels Belgium"},{"name":"Genetic and Epigenetic Alterations of Genomes, de Duve Institute, Faculty of Pharmacy and Biomedical Sciences Universit\u00e9 catholique de Louvain  Brussels 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