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The two proteins function together in a mitochondrial quality control pathway whereby\n                    <jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>\n                    1 accumulates on damaged mitochondria and activates Parkin to induce mitophagy. How\n                    <jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>\n                    1 kinase activity releases the auto\u2010inhibited ubiquitin ligase activity of Parkin remains unclear. Here, we identify a binding switch between phospho\u2010ubiquitin (\n                    <jats:styled-content style=\"fixed-case\">pU<\/jats:styled-content>\n                    b) and the ubiquitin\u2010like domain (Ubl) of Parkin as a key element. By mutagenesis and\n                    <jats:styled-content style=\"fixed-case\">SAXS<\/jats:styled-content>\n                    , we show that\n                    <jats:styled-content style=\"fixed-case\">pU<\/jats:styled-content>\n                    b binds to\n                    <jats:styled-content style=\"fixed-case\">RING<\/jats:styled-content>\n                    1 of Parkin at a site formed by His302 and Arg305.\n                    <jats:styled-content style=\"fixed-case\">pU<\/jats:styled-content>\n                    b binding promotes disengagement of the Ubl from\n                    <jats:styled-content style=\"fixed-case\">RING<\/jats:styled-content>\n                    1 and subsequent Parkin phosphorylation. A crystal structure of Parkin \u039486\u2013130 at 2.54\u00a0\u00c5 resolution allowed the design of mutations that specifically release the Ubl domain from\n                    <jats:styled-content style=\"fixed-case\">RING<\/jats:styled-content>\n                    1. These mutations mimic\n                    <jats:styled-content style=\"fixed-case\">pU<\/jats:styled-content>\n                    b binding and promote Parkin phosphorylation. Measurements of the E2 ubiquitin\u2010conjugating enzyme UbcH7 binding to Parkin and Parkin E3\u00a0ligase activity suggest that Parkin phosphorylation regulates E3\u00a0ligase activity downstream of\n                    <jats:styled-content style=\"fixed-case\">pU<\/jats:styled-content>\n                    b binding.\n                  <\/jats:p>","DOI":"10.15252\/embj.201592237","type":"journal-article","created":{"date-parts":[[2015,8,7]],"date-time":"2015-08-07T22:09:19Z","timestamp":1438985359000},"page":"2492-2505","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":197,"title":["A Ubl\/ubiquitin switch in the activation of Parkin"],"prefix":"10.1038","volume":"34","author":[{"given":"V\u00e9ronique","family":"Sauv\u00e9","sequence":"first","affiliation":[{"name":"Groupe de recherch\u00e9 ax\u00e9 sur la structure des prot\u00e9ines and Department of Biochemistry McGill University Montr\u00e9al QC Canada"}]},{"given":"Asparouh","family":"Lilov","sequence":"additional","affiliation":[{"name":"Groupe de recherch\u00e9 ax\u00e9 sur la structure des prot\u00e9ines and Department of Biochemistry McGill University Montr\u00e9al QC Canada"}]},{"given":"Marjan","family":"Seirafi","sequence":"additional","affiliation":[{"name":"Groupe de recherch\u00e9 ax\u00e9 sur la structure des prot\u00e9ines and Department of Biochemistry McGill University Montr\u00e9al QC Canada"}]},{"given":"Marta","family":"Vranas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics McGill University Montr\u00e9al QC Canada"}]},{"given":"Shafqat","family":"Rasool","sequence":"additional","affiliation":[{"name":"Groupe de recherch\u00e9 ax\u00e9 sur la structure des prot\u00e9ines and Department of Biochemistry McGill University Montr\u00e9al QC Canada"},{"name":"Department of Pharmacology and Therapeutics McGill University Montr\u00e9al QC Canada"}]},{"given":"Guennadi","family":"Kozlov","sequence":"additional","affiliation":[{"name":"Groupe de recherch\u00e9 ax\u00e9 sur la structure des prot\u00e9ines and Department of Biochemistry McGill University Montr\u00e9al QC Canada"}]},{"given":"Tara","family":"Sprules","sequence":"additional","affiliation":[{"name":"Quebec\/Eastern Canada High Field NMR Facility (QANUC) Montr\u00e9al QC Canada"}]},{"given":"Jimin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry Yale University New Haven CT USA"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Trempe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics McGill University Montr\u00e9al QC Canada"}]},{"given":"Kalle","family":"Gehring","sequence":"additional","affiliation":[{"name":"Groupe de recherch\u00e9 ax\u00e9 sur la structure des prot\u00e9ines and Department of Biochemistry McGill University Montr\u00e9al QC 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