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Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin‐like domain
Author(s) -
Sakata Eri,
Yamaguchi Yoshiki,
Kurimoto Eiji,
Kikuchi Jun,
Yokoyama Shigeyuki,
Yamada Shingo,
Kawahara Hiroyuki,
Yokosawa Hideyoshi,
Hattori Nobutaka,
Mizuno Yoshikuni,
Tanaka Keiji,
Kato Koichi
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.embor764
Subject(s) - parkin , ubiquitin ligase , ubiquitin , proteasome , mutation , protein subunit , point mutation , chemistry , biology , genetics , microbiology and biotechnology , parkinson's disease , gene , medicine , disease , pathology
Parkin, a product of the causative gene of autosomal‐recessive juvenile parkinsonism (AR‐JP), is a RING‐type E3 ubiquitin ligase and has an amino‐terminal ubiquitin‐like (Ubl) domain. Although a single mutation that causes an Arg to Pro substitution at position 42 of the Ubl domain (the Arg 42 mutation) has been identified in AR‐JP patients, the function of this domain is not clear. In this study, we determined the three‐dimensional structure of the Ubl domain of parkin by NMR, in particular by extensive use of backbone 15 N‐ 1 H residual dipolar‐coupling data. Inspection of chemical‐shift‐perturbation data showed that the parkin Ubl domain binds the Rpn10 subunit of 26S proteasomes via the region of parkin that includes position 42. Our findings suggest that the Arg 42 mutation induces a conformational change in the Rpn10‐binding site of Ubl, resulting in impaired proteasomal binding of parkin, which could be the cause of AR‐JP.