Lipidation by the host prenyltransferase machinery facilitates membrane localization of Legionella pneumophila effector proteins.
The intracellular human pathogen Legionella pneumophila translocates multiple proteins in the host cytosol known as effectors, which subvert host cellular processes to create a membrane-bound organelle that supports bacterial replication. It was observed that several Legionella effectors encode a prototypical eukaryotic prenylation CAAX motif (where C represents a cysteine residue and A denotes an aliphatic amino acid). These bacterial motifs mediated posttranslational modification of effector proteins resulting in the addition of either a farnesyl or geranylgeranyl isoprenyl lipid moiety to the cysteine residue of the CAAX tetrapeptide. Lipidation enhanced membrane affinity for most Legionella CAAX motif proteins and facilitated the localization of these effector proteins to host organelles. Host farnesyltransferase and class I geranylgeranyltransferase were both involved in the lipidation of the Legionella CAAX motif proteins. Perturbation of the host prenylation machinery during infection adversely affected the remodeling of the Legionella-containing vacuole. Thus, these data indicate that Legionella utilize the host prenylation machinery to facilitate targeting of effector proteins to membrane-bound organelles during intracellular infection.
Ivanov
Stanimir S
SS
Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Charron
Guillaume
G
Hang
Howard C
HC
Roy
Craig R
CR
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004122:Dimethylallyltranstransferase / Q000235:genetics / Q000378:metabolism*; D004224:Diterpenes / Q000378:metabolism; D005204:Farnesol / Q000378:metabolism; D051231:Farnesyltranstransferase / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D016952:Legionella pneumophila / Q000502:physiology*; D007877:Legionnaires' Disease / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017368:Protein Prenylation
D001426:Bacterial Proteins; D004224:Diterpenes; D005204:Farnesol; C017338:geranylgeraniol; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D004122:Dimethylallyltranstransferase; D051231:Farnesyltranstransferase
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