Parkin Binds the Rpn10 Subunit of 26S Proteasomes Through Its Ubiquitin-like Domain

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2003 Mar 14

PMID 12634850

Citations 80

Authors

Eri Sakata

Yoshiki Yamaguchi

Eiji Kurimoto

Jun Kikuchi

Shigeyuki Yokoyama

Shingo Yamada

Hiroyuki Kawahara

Hideyoshi Yokosawa

Nobutaka Hattori

Yoshikuni Mizuno

Keiji Tanaka

Koichi Kato

Affiliations

Soon will be listed here.

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.

Citing Articles

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