Reversible phosphocholination of Rab proteins by Legionella pneumophila effector proteins
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Reversible phosphocholination of Rab proteins by Legionella pneumophila effector proteins. / Goody, Philip R; Heller, Katharina; Oesterlin, Lena K; Itzen, Aymelt; Goody, Roger S.
in: EMBO J, Jahrgang 31, Nr. 7, 04.04.2012, S. 1774-84.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Reversible phosphocholination of Rab proteins by Legionella pneumophila effector proteins
AU - Goody, Philip R
AU - Heller, Katharina
AU - Oesterlin, Lena K
AU - Itzen, Aymelt
AU - Goody, Roger S
PY - 2012/4/4
Y1 - 2012/4/4
N2 - The Legionella pneumophila protein AnkX that is injected into infected cells by a Type IV secretion system transfers a phosphocholine group from CDP-choline to a serine in the Rab1 and Rab35 GTPase Switch II regions. We show here that the consequences of phosphocholination on the interaction of Rab1/Rab35 with various partner proteins are quite distinct. Activation of phosphocholinated Rabs by GTP/GDP exchange factors (GEFs) and binding to the GDP dissociation inhibitor (GDI) are strongly inhibited, whereas deactivation by GTPase activating proteins (GAPs) and interactions with Rab-effector proteins (such as LidA and MICAL-3) are only slightly inhibited. We show that the Legionella protein lpg0696 has the ability to remove the phosphocholine group from Rab1. We present a model in which the action of AnkX occurs as an alternative to GTP/GDP exchange, stabilizing phosphocholinated Rabs in membranes in the GDP form because of loss of GDI binding ability, preventing interactions with cellular GTPase effectors, which require the GTP-bound form. Generation of the GTP form of phosphocholinated Rab proteins cannot occur due to loss of interaction with cellular GEFs.
AB - The Legionella pneumophila protein AnkX that is injected into infected cells by a Type IV secretion system transfers a phosphocholine group from CDP-choline to a serine in the Rab1 and Rab35 GTPase Switch II regions. We show here that the consequences of phosphocholination on the interaction of Rab1/Rab35 with various partner proteins are quite distinct. Activation of phosphocholinated Rabs by GTP/GDP exchange factors (GEFs) and binding to the GDP dissociation inhibitor (GDI) are strongly inhibited, whereas deactivation by GTPase activating proteins (GAPs) and interactions with Rab-effector proteins (such as LidA and MICAL-3) are only slightly inhibited. We show that the Legionella protein lpg0696 has the ability to remove the phosphocholine group from Rab1. We present a model in which the action of AnkX occurs as an alternative to GTP/GDP exchange, stabilizing phosphocholinated Rabs in membranes in the GDP form because of loss of GDI binding ability, preventing interactions with cellular GTPase effectors, which require the GTP-bound form. Generation of the GTP form of phosphocholinated Rab proteins cannot occur due to loss of interaction with cellular GEFs.
KW - Bacterial Proteins
KW - GTP Phosphohydrolases
KW - GTPase-Activating Proteins
KW - Guanine Nucleotide Exchange Factors
KW - Legionella pneumophila
KW - Phosphorylcholine
KW - rab GTP-Binding Proteins
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/emboj.2012.16
DO - 10.1038/emboj.2012.16
M3 - SCORING: Journal article
C2 - 22307087
VL - 31
SP - 1774
EP - 1784
JO - EMBO J
JF - EMBO J
SN - 0261-4189
IS - 7
ER -