4BM9

Structure of the autoinhibited Parkin catalytic domain

4BM9 の概要

• エントリーDOI: 10.2210/pdb4bm9/pdb
• 分子名称: E3 UBIQUITIN-PROTEIN LIGASE PARKIN, ZINC ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: ligase, neurodegenerative disease
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm, cytosol: O60260
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37724.61

構造登録者

Wauer, T.,Komander, D. (登録日: 2013-05-07, 公開日: 2013-06-12, 最終更新日: 2024-05-08)

主引用文献

Wauer, T.,Komander, D.
Structure of the Human Parkin Ligase Domain in an Autoinhibited State.
Embo J., 32:2099-, 2013

PubMed Abstract: Mutations in the protein Parkin are associated with Parkinson's disease (PD), the second most common neurodegenerative disease in men. Parkin is an E3 ubiquitin (Ub) ligase of the structurally uncharacterized RING-in-between-RING(IBR)-RING (RBR) family, which, in an HECT-like fashion, forms a catalytic thioester intermediate with Ub. We here report the crystal structure of human Parkin spanning the Unique Parkin domain (UPD, also annotated as RING0) and RBR domains, revealing a tightly packed structure with unanticipated domain interfaces. The UPD adopts a novel elongated Zn-binding fold, while RING2 resembles an IBR domain. Two key interactions keep Parkin in an autoinhibited conformation. A linker that connects the IBR with the RING2 over a 50-Å distance blocks the conserved E2∼Ub binding site of RING1. RING2 forms a hydrophobic interface with the UPD, burying the catalytic Cys431, which is part of a conserved catalytic triad. Opening of intra-domain interfaces activates Parkin, and enables Ub-based suicide probes to modify Cys431. The structure further reveals a putative phospho-peptide docking site in the UPD, and explains many PD-causing mutations.

PubMed: 23727886
DOI: 10.1038/EMBOJ.2013.125

実験手法

X-RAY DIFFRACTION (2.25 Å)