4ZYN

Crystal Structure of Parkin E3 ubiquitin ligase (linker deletion; delta 86-130)

4ZYN の概要

• エントリーDOI: 10.2210/pdb4zyn/pdb
• 関連するPDBエントリー: 2ZEQ 4BM9 4I1H 4K7D 4K95
• 分子名称: E3 ubiquitin-protein ligase parkin, ZINC ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: ring domains, ubiquitin-like domain, rbr, ligase
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96290.64

構造登録者

Lilov, A.,Sauve, V.,Trempe, J.F.,Rodionov, D.,Wang, J.,Gehring, K. (登録日: 2015-05-21, 公開日: 2015-08-19, 最終更新日: 2024-11-13)

主引用文献

Sauve, V.,Lilov, A.,Seirafi, M.,Vranas, M.,Rasool, S.,Kozlov, G.,Sprules, T.,Wang, J.,Trempe, J.F.,Gehring, K.
A Ubl/ubiquitin switch in the activation of Parkin.
Embo J., 34:2492-2505, 2015

PubMed Abstract: Mutations in Parkin and PINK1 cause an inherited early-onset form of Parkinson's disease. The two proteins function together in a mitochondrial quality control pathway whereby PINK1 accumulates on damaged mitochondria and activates Parkin to induce mitophagy. How PINK1 kinase activity releases the auto-inhibited ubiquitin ligase activity of Parkin remains unclear. Here, we identify a binding switch between phospho-ubiquitin (pUb) and the ubiquitin-like domain (Ubl) of Parkin as a key element. By mutagenesis and SAXS, we show that pUb binds to RING1 of Parkin at a site formed by His302 and Arg305. pUb binding promotes disengagement of the Ubl from RING1 and subsequent Parkin phosphorylation. A crystal structure of Parkin Δ86-130 at 2.54 Å resolution allowed the design of mutations that specifically release the Ubl domain from RING1. These mutations mimic pUb binding and promote Parkin phosphorylation. Measurements of the E2 ubiquitin-conjugating enzyme UbcH7 binding to Parkin and Parkin E3 ligase activity suggest that Parkin phosphorylation regulates E3 ligase activity downstream of pUb binding.

PubMed: 26254305
DOI: 10.15252/embj.201592237

実験手法

X-RAY DIFFRACTION (2.54 Å)