TY - JOUR
T1 - A Legionella effector ADP-ribosyltransferase inactivates glutamate dehydrogenase
AU - Black, Miles H.
AU - Osinski, Adam
AU - Park, Gina J.
AU - Gradowski, Marcin
AU - Servage, Kelly A.
AU - Pawłowski, Krzysztof
AU - Tagliabracci, Vincent S.
N1 - Publisher Copyright:
© 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology
PY - 2021/1/1
Y1 - 2021/1/1
N2 - ADP-ribosyltransferases (ARTs) are a widespread superfamily of enzymes frequently employed in pathogenic strategies of bacteria. Legionella pneumophila, the causative agent of a severe form of pneumonia known as Legionnaire’s disease, has acquired over 330 translocated effectors that showcase remarkable biochemical and structural diversity. However, the ART effectors that influence L. pneumophila have not been well defined. Here, we took a bioinformatic approach to search the Legionella effector repertoire for additional divergent members of the ART superfamily and identified an ART domain in Legionella pneumophila gene0181, which we hereafter refer to as Legionella ADP-Ribosyltransferase 1 (Lart1) (Legionella ART 1). We show that L. pneumophila Lart1 targets a specific class of 120-kDa NAD+-dependent glutamate dehydrogenase (GDH) enzymes found in fungi and protists, including many natural hosts of Legionella. Lart1 targets a conserved arginine residue in the NAD+-binding pocket of GDH, thereby blocking oxidative deamination of glutamate. Therefore, Lart1 could be the first example of a Legionella effector which directly targets a host metabolic enzyme during infection.
AB - ADP-ribosyltransferases (ARTs) are a widespread superfamily of enzymes frequently employed in pathogenic strategies of bacteria. Legionella pneumophila, the causative agent of a severe form of pneumonia known as Legionnaire’s disease, has acquired over 330 translocated effectors that showcase remarkable biochemical and structural diversity. However, the ART effectors that influence L. pneumophila have not been well defined. Here, we took a bioinformatic approach to search the Legionella effector repertoire for additional divergent members of the ART superfamily and identified an ART domain in Legionella pneumophila gene0181, which we hereafter refer to as Legionella ADP-Ribosyltransferase 1 (Lart1) (Legionella ART 1). We show that L. pneumophila Lart1 targets a specific class of 120-kDa NAD+-dependent glutamate dehydrogenase (GDH) enzymes found in fungi and protists, including many natural hosts of Legionella. Lart1 targets a conserved arginine residue in the NAD+-binding pocket of GDH, thereby blocking oxidative deamination of glutamate. Therefore, Lart1 could be the first example of a Legionella effector which directly targets a host metabolic enzyme during infection.
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U2 - 10.1016/j.jbc.2021.100301
DO - 10.1016/j.jbc.2021.100301
M3 - Article
C2 - 33476647
AN - SCOPUS:85102819376
SN - 0021-9258
VL - 296
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
M1 - 100301
ER -