{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T21:09:09Z","timestamp":1784581749091,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19H05648,JP17H03987,JP16K07284"],"award-info":[{"award-number":["JP19H05648,JP17H03987,JP16K07284"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20am0101083j0004,17gm0810010h0202,21ek0109443h0002"],"award-info":[{"award-number":["20am0101083j0004,17gm0810010h0202,21ek0109443h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Defects in the <jats:italic>O<\/jats:italic>\u2010mannosyl glycan of \u03b1\u2010dystroglycan (\u03b1\u2010DG) are associated with \u03b1\u2010dystroglycanopathy, a group of congenital muscular dystrophies. While \u03b1\u2010DG has many <jats:italic>O<\/jats:italic>\u2010mannosylation sites, only the specific positions can be modified with the functional <jats:italic>O<\/jats:italic>\u2010mannosyl glycan, namely, core M3\u2010type glycan. POMGNT2 is a glycosyltransferase which adds \u03b21,4\u2010linked GlcNAc to the <jats:italic>O<\/jats:italic>\u2010mannose (Man) residue to acquire core M3\u2010type glycan. Although it is assumed that POMGNT2 extends the specific <jats:italic>O<\/jats:italic>\u2010Man residues around particular amino acid sequences, the details are not well understood. Here, we determined a series of crystal structures of POMGNT2 with and without the acceptor <jats:italic>O<\/jats:italic>\u2010mannosyl peptides and identified the critical interactions between POMGNT2 and the acceptor peptide. POMGNT2 has an N\u2010terminal catalytic domain and a C\u2010terminal fibronectin type III (FnIII) domain and forms a dimer. The acceptor peptide is sandwiched between the two protomers. The catalytic domain of one protomer recognizes the <jats:italic>O<\/jats:italic>\u2010mannosylation site (TPT motif), and the FnIII domain of the other protomer recognizes the C\u2010terminal region of the peptide. Structure\u2010based mutational studies confirmed that amino acid residues of the catalytic domain interacting with mannose or the TPT motif are essential for POMGNT2 enzymatic activity. In addition, the FnIII domain is also essential for the activity and it interacts with the peptide mainly by hydrophobic interaction. Our study provides the first atomic\u2010resolution insights into specific acceptor recognition by the FnIII domain of POMGNT2. The catalytic mechanism of POMGNT2 is proposed based on the structure.<\/jats:p>","DOI":"10.1111\/gtc.12853","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T00:36:20Z","timestamp":1619224580000},"page":"485-494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The structure of POMGNT2 provides new insights into the mechanism to determine the functional <i>O<\/i>\u2010mannosylation site on \u03b1\u2010dystroglycan"],"prefix":"10.1111","volume":"26","author":[{"given":"Rieko","family":"Imae","sequence":"first","affiliation":[{"name":"Molecular Glycobiology Research Team for Mechanism of Aging Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Itabashi\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Kuwabara","sequence":"additional","affiliation":[{"name":"High Energy Accelerator Research Organization (KEK) Institute of Materials Structure Science Structural Biology Research Center Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Manya","sequence":"additional","affiliation":[{"name":"Molecular Glycobiology Research Team for Mechanism of Aging Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Itabashi\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Glyco\u2010organic Chemistry The Noguchi Institute Itabashi\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Tsuyuguchi","sequence":"additional","affiliation":[{"name":"High Energy Accelerator Research Organization (KEK) Institute of Materials Structure Science Structural Biology Research Center Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Laboratory of Glyco\u2010organic Chemistry The Noguchi Institute Itabashi\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamao","family":"Endo","sequence":"additional","affiliation":[{"name":"Molecular Glycobiology Research Team for Mechanism of Aging Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Itabashi\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-2896","authenticated-orcid":false,"given":"Ryuichi","family":"Kato","sequence":"additional","affiliation":[{"name":"High Energy Accelerator Research Organization (KEK) Institute of Materials Structure Science Structural Biology Research Center Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth070"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwj016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00034-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.4.2156"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.95.004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.764712"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1114836108"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cws002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3749"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300480200"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214115"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.02.017"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.05.022"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14220-z"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.061005.092322"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09638"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218620110"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307228101"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2017.06.024"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.751917"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.07.009"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2016.1184224"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwt116"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020437"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwq082"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03943"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwx062"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.126474"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2019.151106"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03941"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03288"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00070-3"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1239951"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwv021"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1180512"}],"container-title":["Genes to Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gtc.12853","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/gtc.12853","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gtc.12853","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T23:32:04Z","timestamp":1693351924000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gtc.12853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":35,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1111\/gtc.12853"],"URL":"https:\/\/doi.org\/10.1111\/gtc.12853","archive":["Portico"],"relation":{},"ISSN":["1356-9597","1365-2443"],"issn-type":[{"value":"1356-9597","type":"print"},{"value":"1365-2443","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,20]]},"assertion":[{"value":"2021-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}