1iyf
From Proteopedia
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'''Solution structure of ubiquitin-like domain of human parkin'''<br /> | '''Solution structure of ubiquitin-like domain of human parkin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Parkin, a product of the causative gene of autosomal-recessive juvenile | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IYF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] Full crystallographic information is available from [http:// | + | 1IYF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IYF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Kurimoto, E.]] | [[Category: Kurimoto, E.]] | ||
[[Category: Mizuno, Y.]] | [[Category: Mizuno, Y.]] | ||
| - | [[Category: RSGI, RIKEN | + | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] |
[[Category: Sakata, E.]] | [[Category: Sakata, E.]] | ||
[[Category: Tanaka, K.]] | [[Category: Tanaka, K.]] | ||
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[[Category: ubiquitin fold]] | [[Category: ubiquitin fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:17:00 2008'' |
Revision as of 11:17, 21 February 2008
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Solution structure of ubiquitin-like domain of human parkin
Contents |
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 Thu Feb 21 13:17:00 2008
Categories: Homo sapiens | Single protein | Ubiquitin--protein ligase | Hattori, N. | Kato, K. | Kawahara, H. | Kikuchi, J. | Kurimoto, E. | Mizuno, Y. | RSGI, RIKEN Structural Genomics/Proteomics Initiative. | Sakata, E. | Tanaka, K. | Yamaguchi, Y. | Yokosawa, H. | Yokoyama, S. | Riken structural genomics/proteomics initiative | Rsgi | Structural genomics | Ubiquitin fold
