1iyf

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Solution structure of ubiquitin-like domain of human parkin

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Adenocarcinoma of lung, somatic OMIM:[602544], Adenocarcinoma, ovarian, somatic OMIM:[602544], Leprosy, susceptibility to OMIM:[602544], Parkinson disease, juvenile, type 2 OMIM:[602544]

About this Structure

1IYF is a Single protein structure of sequence from Homo sapiens. Active as Ubiquitin--protein ligase, with EC number 6.3.2.19 Full crystallographic information is available from OCA.

Reference

Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain., Sakata E, Yamaguchi Y, Kurimoto E, Kikuchi J, Yokoyama S, Yamada S, Kawahara H, Yokosawa H, Hattori N, Mizuno Y, Tanaka K, Kato K, EMBO Rep. 2003 Mar;4(3):301-6. PMID:12634850

Page seeded by OCA on Mon Nov 12 17:35:50 2007