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Legionella effector LpPIP recruits protein phosphatase 1 to the mitochondria to induce dephosphorylation of outer membrane proteins

ABSTRACT: Legionella pneumophila utilises a type IVB secretion system (T4SS) to translocate over 300 effectors into host cells, hijacking cellular processes, including those within the mitochondrion. Currently, no Legionella effectors have been identified at the mitochondrial outer membrane, a critical interface between the organelle and rest of the cell. We screened the Legionella effector repertoire for features of mitochondrial tail-anchored (TA) proteins and identified four putative TA effectors. Among them, Lpg1625 was confirmed to localize to the mitochondrial outer membrane and shown to interact with all three isoforms of protein phosphatase 1 (PP1) through an RVxF motif. Importantly, PP1 remains catalytically active upon interaction with Lpg1625, leading to dephosphorylation of specific mitochondrial outer membrane proteins. Altering the TA signature to direct Lpg1625 to the ER led to ER-recruitment of PP1 and subsequent dephosphorylation of ER resident proteins indicating that Lpg1625 controls PP1 localisation and not substrate specificity. This study uncovers a novel pathogen-mediated strategy to modulate PP1 and manipulate the host phosphoproteome.

INSTRUMENT(S): Orbitrap Eclipse, Orbitrap Ascend, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Epithelial Cell

DISEASE(S): Legionnaires' Disease,Legionellosis,Pontiac Fever

SUBMITTER: Kai Qi Yek

LAB HEAD: Diana Stojanovski

PROVIDER: PXD057005 | Pride | 2025-06-03

REPOSITORIES: Pride

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