{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:56:04Z","timestamp":1791158164663,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"30","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,7,26]]},"abstract":"<jats:p>\n                    The Josephin domain plays an important role in the cellular functions of ataxin-3, the protein responsible for the neurodegenerative Machado\u2013Joseph disease. We have determined the solution structure of Josephin and shown that it belongs to the family of papain-like cysteine proteases, sharing the highest degree of structural similarity with bacterial staphopain. A currently unique structural feature of Josephin is a flexible helical hairpin formed by a 32-residue insertion, which could determine substrate specificity. By using the Josephin structure and the availability of NMR chemical shift assignments, we have mapped the enzyme active site by using the typical cysteine protease inhibitors, transepoxysuccinyl-\n                    <jats:sc>l<\/jats:sc>\n                    -eucylamido-4-guanidino-butane (E-64) and [\n                    <jats:sc>l<\/jats:sc>\n                    -3-trans-(propylcarbamyl)oxirane-2-carbonyl]-\n                    <jats:sc>l<\/jats:sc>\n                    -isoleucyl-\n                    <jats:sc>l<\/jats:sc>\n                    -proline (CA-074). We also demonstrate that the specific interaction of Josephin with the ubiquitin-like domain of the ubiquitin- and proteasome-binding factor HHR23B involves complementary exposed hydrophobic surfaces. The structural similarity with other deubiquitinating enzymes suggests a model for the proteolytic enzymatic activity of ataxin-3.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0501732102","type":"journal-article","created":{"date-parts":[[2005,7,14]],"date-time":"2005-07-14T20:24:52Z","timestamp":1121372692000},"page":"10493-10498","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":169,"title":["The solution structure of the Josephin domain of ataxin-3: Structural determinants for molecular recognition"],"prefix":"10.1073","volume":"102","author":[{"given":"Giuseppe","family":"Nicastro","sequence":"first","affiliation":[{"name":"National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom; School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom; and Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh P.","family":"Menon","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom; School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom; and Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Masino","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom; School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom; and Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip P.","family":"Knowles","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom; School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom; and Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil Q.","family":"McDonald","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom; School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom; and Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Pastore","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom; School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom; and Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,7,14]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1194-221"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067122"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310939200"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1530212100"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg344"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.12.1795"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.18.6469-6483.2003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205259200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(01)02065-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00748-8"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg297"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.131"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.09.065"},{"key":"e_1_3_2_14_2","first-page":"102","volume":"49","year":"1993","unstructured":"Hofmann, B., Schomburg, D. & Hecht, H. J. (1993) Acta Crystallogr. A 49, Suppl., 102.","journal-title":"Acta Crystallogr. A"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2036536100"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10858-004-4343-3"},{"key":"e_1_3_2_17_2","first-page":"277","volume":"3","year":"1995","unstructured":"Delaglio, F., Grzesiek, S., Vuister, G. W., Pfeifer, F. & Bax, A. (1995) J. Biomol. NMR 3, 277-293.","journal-title":"J. Biomol. NMR"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227465"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.699"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026703605147"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00449a003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2614(90)85567-V"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-0278(97)00028-X"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444998003254"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892009944"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(90)80070-V"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/73331"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307200200"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja026939x"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00662a014"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1489"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98753-3"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.13.3787"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.14.3877"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.2004.04245.x"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.0083"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00659-1"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr950025u"},{"key":"e_1_3_2_40_2","first-page":"244","volume":"1597","year":"2002","unstructured":"Yamamoto, A., Tomoo, K., Matsugi, K., Hara, T., In, Y., Murata, M., Kitamura, K. & Ishida, T. (2002) Biophys. Biochem. Acta 1597, 244-251.","journal-title":"Biophys. Biochem. Acta"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(67)80055-X"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi011892y"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304628200"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01199-6"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407965101"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309448200"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0501732102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T13:48:15Z","timestamp":1649771295000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0501732102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7,14]]},"references-count":46,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2005,7,26]]}},"alternative-id":["10.1073\/pnas.0501732102"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0501732102","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,7,14]]},"assertion":[{"value":"2005-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-06-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-07-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}