Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 430, Issue 17, Pages 2843-2856Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2018.05.043
Keywords
Legionella pneumophila; mART; NAD(+); SdeA; ubiquitin
Categories
Funding
- International Collaborative Research Program of Institute for Protein Research, Osaka University [ICR-17-05]
- POSCO Science Fellowship of POSCO TJ Park Foundation
- Samsung Science & Technology Foundation [SSTF-BA 1701-14]
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Conventional ubiquitylation occurs through an ATP-dependent three-enzyme cascade (E1, E2, and E3) that mediates the covalent conjugation of the C-terminus of ubiquitin to a lysine on the substrate. SdeA, which belongs to the SidE effector family of Legionella pneumophila, can transfer ubiquitin to endoplasmic reticulum-associated Rab-family GTPases in a manner independent of El and E2 enzymes. The novel ubiquitin-modifying enzyme SdeA utilizes NAD(+) as a cofactor to attach ubiquitin to a serine residue of the substrate. Here, to elucidate the coupled enzymatic reaction of NAD+ hydrolysis and ADP-ribosylation of ubiquitin in SdeA, we characterized the mono-ADP-ribosyltransferase domain of SdeA and show that it consists of two sub-domains termed mART-N and mART-C. The crystal structure of the mART-C domain of SdeA was also determined in free form and in complex with NAD(+) at high resolution. Furthermore, the spatial orientations of the N-terminal deubiquitylase, phosphodiesterase, mono-ADP-ribosyltransferase, and C-terminal coiled-coil domains within the 180-kDa full-length SdeA were determined. These results provide insight into the unusual ubiquitylation mechanism of SdeA and expand our knowledge on the structure-function of mono-ADP-ribosyltransferases. (C) 2018 Elsevier Ltd. All rights reserved.
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