Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b
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Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b. / Kaspers, Marietta S; Pogenberg, Vivian; Pett, Christian; Ernst, Stefan; Ecker, Felix; Ochtrop, Philipp; Groll, Michael; Hedberg, Christian; Itzen, Aymelt.
in: NAT COMMUN, Jahrgang 14, Nr. 1, 19.04.2023, S. 2245.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b
AU - Kaspers, Marietta S
AU - Pogenberg, Vivian
AU - Pett, Christian
AU - Ernst, Stefan
AU - Ecker, Felix
AU - Ochtrop, Philipp
AU - Groll, Michael
AU - Hedberg, Christian
AU - Itzen, Aymelt
N1 - © 2023. The Author(s).
PY - 2023/4/19
Y1 - 2023/4/19
N2 - Bacterial pathogens often make use of post-translational modifications to manipulate host cells. Legionella pneumophila, the causative agent of Legionnaires disease, secretes the enzyme AnkX that uses cytidine diphosphate-choline to post-translationally modify the human small G-Protein Rab1 with a phosphocholine moiety at Ser76. Later in the infection, the Legionella enzyme Lem3 acts as a dephosphocholinase, hydrolytically removing the phosphocholine. While the molecular mechanism for Rab1 phosphocholination by AnkX has recently been resolved, structural insights into the activity of Lem3 remained elusive. Here, we stabilise the transient Lem3:Rab1b complex by substrate mediated covalent capture. Through crystal structures of Lem3 in the apo form and in complex with Rab1b, we reveal Lem3's catalytic mechanism, showing that it acts on Rab1 by locally unfolding it. Since Lem3 shares high structural similarity with metal-dependent protein phosphatases, our Lem3:Rab1b complex structure also sheds light on how these phosphatases recognise protein substrates.
AB - Bacterial pathogens often make use of post-translational modifications to manipulate host cells. Legionella pneumophila, the causative agent of Legionnaires disease, secretes the enzyme AnkX that uses cytidine diphosphate-choline to post-translationally modify the human small G-Protein Rab1 with a phosphocholine moiety at Ser76. Later in the infection, the Legionella enzyme Lem3 acts as a dephosphocholinase, hydrolytically removing the phosphocholine. While the molecular mechanism for Rab1 phosphocholination by AnkX has recently been resolved, structural insights into the activity of Lem3 remained elusive. Here, we stabilise the transient Lem3:Rab1b complex by substrate mediated covalent capture. Through crystal structures of Lem3 in the apo form and in complex with Rab1b, we reveal Lem3's catalytic mechanism, showing that it acts on Rab1 by locally unfolding it. Since Lem3 shares high structural similarity with metal-dependent protein phosphatases, our Lem3:Rab1b complex structure also sheds light on how these phosphatases recognise protein substrates.
KW - Humans
KW - Legionella/metabolism
KW - Phosphorylcholine/metabolism
KW - Legionella pneumophila/metabolism
KW - Legionnaires' Disease
KW - Protein Processing, Post-Translational
KW - Bacterial Proteins/metabolism
KW - rab1 GTP-Binding Proteins/metabolism
U2 - 10.1038/s41467-023-37621-7
DO - 10.1038/s41467-023-37621-7
M3 - SCORING: Journal article
C2 - 37076474
VL - 14
SP - 2245
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -