{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:53:14Z","timestamp":1791726794450,"version":"4.3.4"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"15","license":[{"start":{"date-parts":[[2013,5,31]],"date-time":"2013-05-31T00:00:00Z","timestamp":1369958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2013,5,31]],"date-time":"2013-05-31T00:00:00Z","timestamp":1369958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2013,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutations in the protein Parkin are associated with Parkinson's disease (PD), the second most common neurodegenerative disease in men. Parkin is an E3 ubiquitin (Ub) ligase of the structurally uncharacterized RING\u2010in\u2010between\u2010RING(IBR)\u2010RING (RBR) family, which, in an HECT\u2010like fashion, forms a catalytic thioester intermediate with Ub. We here report the crystal structure of human Parkin spanning the Unique Parkin domain (UPD, also annotated as RING0) and RBR domains, revealing a tightly packed structure with unanticipated domain interfaces. The UPD adopts a novel elongated Zn\u2010binding fold, while RING2 resembles an IBR domain. Two key interactions keep Parkin in an autoinhibited conformation. A linker that connects the IBR with the RING2 over a 50\u2010\u00c5 distance blocks the conserved E2\u223cUb binding site of RING1. RING2 forms a hydrophobic interface with the UPD, burying the catalytic Cys431, which is part of a conserved catalytic triad. Opening of intra\u2010domain interfaces activates Parkin, and enables Ub\u2010based suicide probes to modify Cys431. The structure further reveals a putative phospho\u2010peptide docking site in the UPD, and explains many PD\u2010causing mutations.<\/jats:p>","DOI":"10.1038\/emboj.2013.125","type":"journal-article","created":{"date-parts":[[2013,5,31]],"date-time":"2013-05-31T10:03:12Z","timestamp":1369994592000},"page":"2099-2112","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":327,"title":["Structure of the human Parkin ligase domain in an autoinhibited state"],"prefix":"10.1038","volume":"32","author":[{"given":"Tobias","family":"Wauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Komander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,5,31]]},"reference":[{"key":"BFEMBJ2013125_CR1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ymeth.2011.07.005","volume":"55","author":"PD Adams","year":"2011","unstructured":"Adams PD, Afonine PV, Bunk\u00f3czi G, Chen VB, Echols N, Headd JJ, Hung L\u2010W, Jain S, Kapral GJ, Grosse Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner RD, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH (2011) The Phenix software for automated determination of macromolecular structures. 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