Abstract
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.
Bibliography
Sakata, E., Yamaguchi, Y., Kurimoto, E., Kikuchi, J., Yokoyama, S., Yamada, S., Kawahara, H., Yokosawa, H., Hattori, N., Mizuno, Y., Tanaka, K., & Kato, K. (2003). Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitinâlike domain. EMBO Reports, 4(3), 301â306. Portico.
Authors
12
- Eri Sakata (first)
- Yoshiki Yamaguchi (additional)
- Eiji Kurimoto (additional)
- Jun Kikuchi (additional)
- Shigeyuki Yokoyama (additional)
- Shingo Yamada (additional)
- Hiroyuki Kawahara (additional)
- Hideyoshi Yokosawa (additional)
- Nobutaka Hattori (additional)
- Yoshikuni Mizuno (additional)
- Keiji Tanaka (additional)
- Koichi Kato (additional)
References
35
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Dates
Type | When |
---|---|
Created | 22 years, 5 months ago (March 12, 2003, 4:41 p.m.) |
Deposited | 1 year, 8 months ago (Dec. 18, 2023, 3:55 p.m.) |
Indexed | 1 hour, 3 minutes ago (Aug. 29, 2025, 5:34 a.m.) |
Issued | 22 years, 6 months ago (Feb. 21, 2003) |
Published | 22 years, 6 months ago (Feb. 21, 2003) |
Published Online | 22 years, 6 months ago (Feb. 21, 2003) |
Published Print | 22 years, 5 months ago (March 1, 2003) |
@article{Sakata_2003, title={Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin‐like domain}, volume={4}, ISSN={1469-3178}, url={http://dx.doi.org/10.1038/sj.embor.embor764}, DOI={10.1038/sj.embor.embor764}, number={3}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Sakata, Eri and Yamaguchi, Yoshiki and Kurimoto, Eiji and Kikuchi, Jun and Yokoyama, Shigeyuki and Yamada, Shingo and Kawahara, Hiroyuki and Yokosawa, Hideyoshi and Hattori, Nobutaka and Mizuno, Yoshikuni and Tanaka, Keiji and Kato, Koichi}, year={2003}, month=feb, pages={301–306} }