2M48

Solution Structure of IBR-RING2 Tandem Domain from Parkin

2M48 の概要

• エントリーDOI: 10.2210/pdb2m48/pdb
• 関連するPDBエントリー: 1WD2 2JMO
• NMR情報: BMRB: 18990
• 分子名称: E3 UBIQUITIN-PROTEIN LIGASE PARKIN, ZINC ION (2 entities in total)
• 機能のキーワード: parkin, ring, ibr, e3 ligase, zn-binding, ligase
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15722.21

構造登録者

Noh, Y.J.,Mercier, P.,Spratt, D.E.,Shaw, G.S. (登録日: 2013-01-30, 公開日: 2013-05-15, 最終更新日: 2024-05-15)

主引用文献

Spratt, D.E.,Julio Martinez-Torres, R.,Noh, Y.J.,Mercier, P.,Manczyk, N.,Barber, K.R.,Aguirre, J.D.,Burchell, L.,Purkiss, A.,Walden, H.,Shaw, G.S.
A molecular explanation for the recessive nature of parkin-linked Parkinson's disease.
Nat Commun, 4:1983-1983, 2013

PubMed Abstract: Mutations in the park2 gene, encoding the RING-inBetweenRING-RING E3 ubiquitin ligase parkin, cause 50% of autosomal recessive juvenile Parkinsonism cases. More than 70 known pathogenic mutations occur throughout parkin, many of which cluster in the inhibitory amino-terminal ubiquitin-like domain, and the carboxy-terminal RING2 domain that is indispensable for ubiquitin transfer. A structural rationale showing how autosomal recessive juvenile Parkinsonism mutations alter parkin function is still lacking. Here we show that the structure of parkin RING2 is distinct from canonical RING E3 ligases and lacks key elements required for E2-conjugating enzyme recruitment. Several pathogenic mutations in RING2 alter the environment of a single surface-exposed catalytic cysteine to inhibit ubiquitination. Native parkin adopts a globular inhibited conformation in solution facilitated by the association of the ubiquitin-like domain with the RING-inBetweenRING-RING C-terminus. Autosomal recessive juvenile Parkinsonism mutations disrupt this conformation. Finally, parkin autoubiquitinates only in cis, providing a molecular explanation for the recessive nature of autosomal recessive juvenile Parkinsonism.

PubMed: 23770917
DOI: 10.1038/ncomms2983

実験手法

SOLUTION NMR