Details

Autor(en) / Beteiligte

• Akturk, Anil
• Wasilko, David J
• Wu, Xiaochun
• Liu, Yao
• Zhang, Yong
• Qiu, Jiazhang
• Luo, Zhao-Qing
• Reiter, Katherine H
• Brzovic, Peter S
• Klevit, Rachel E
• Mao, Yuxin

Titel

Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector

Ist Teil von

• Nature (London), 2018-05, Vol.557 (7707), p.729-733

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Beschreibungen/Notizen

• 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.