6B7P

Crystal structure of Legionella effector sdeD (lpg2509)

6B7P の概要

• エントリーDOI: 10.2210/pdb6b7p/pdb
• 分子名称: SdeD (2 entities in total)
• 機能のキーワード: legionella, ubiquitin, sded, adpr-ub, pr-ub, phosphodiesterase, cell invasion
• 由来する生物種: Legionella pneumophila
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 86878.03

構造登録者

Mao, Y.,Akturk, A.,Wasilko, J. (登録日: 2017-10-04, 公開日: 2018-04-18, 最終更新日: 2024-03-13)

主引用文献

Akturk, A.,Wasilko, D.J.,Wu, X.,Liu, Y.,Zhang, Y.,Qiu, J.,Luo, Z.Q.,Reiter, K.H.,Brzovic, P.S.,Klevit, R.E.,Mao, Y.
Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector.
Nature, 557:729-733, 2018

PubMed Abstract: Ubiquitination is a post-translational modification that regulates many cellular processes in eukaryotes. The conventional ubiquitination cascade culminates in a covalent linkage between the C terminus of ubiquitin (Ub) and a target protein, usually on a lysine side chain. Recent studies of the Legionella pneumophila SidE family of effector proteins revealed a ubiquitination method in which a phosphoribosyl ubiquitin (PR-Ub) is conjugated to a serine residue on substrates via a phosphodiester bond. Here we present the crystal structure of a fragment of the SidE family member SdeA that retains ubiquitination activity, and determine the mechanism of this unique post-translational modification. The structure reveals that the catalytic module contains two distinct functional units: a phosphodiesterase domain and a mono-ADP-ribosyltransferase domain. Biochemical analysis shows that the mono-ADP-ribosyltransferase domain-mediated conversion of Ub to ADP-ribosylated Ub (ADPR-Ub) and the phosphodiesterase domain-mediated ligation of PR-Ub to substrates are two independent activities of SdeA. Furthermore, we present two crystal structures of a homologous phosphodiesterase domain from the SidE family member SdeD in complexes with Ub and ADPR-Ub. The structures suggest a mechanism for how SdeA processes ADPR-Ub to PR-Ub and AMP, and conjugates PR-Ub to a serine residue in substrates. Our study establishes the molecular mechanism of phosphoribosyl-linked ubiquitination and will enable future studies of this unusual type of ubiquitination in eukaryotes.

PubMed: 29795346
DOI: 10.1038/s41586-018-0147-6

実験手法

X-RAY DIFFRACTION (1.51 Å)