title: Lipidation by the host prenyltransferase machinery facilitates membrane localization of Legionella pneumophila effector proteins.
abstract: 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.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
authors.forename: Stanimir S
authors.initials: SS
authors.lastname: Ivanov
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charron
authors.forename: Howard C
authors.initials: HC
authors.lastname: Hang
authors.forename: Craig R
authors.initials: CR
authors.lastname: Roy
mesh_terms: 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
chemical_list: D001426:Bacterial Proteins; D004224:Diterpenes; D005204:Farnesol; C017338:geranylgeraniol; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D004122:Dimethylallyltranstransferase; D051231:Farnesyltranstransferase
references.citation: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1669-74
references.pmid: 9465074
references.citation: Mol Microbiol. 1998 May;28(3):663-74
references.pmid: 9632267
references.citation: J Exp Med. 1983 Oct 1;158(4):1319-31
references.pmid: 6619736
references.citation: Mol Microbiol. 2005 May;56(4):918-33
references.pmid: 15853880
references.citation: PLoS Pathog. 2007 Dec;3(12):e188
references.pmid: 18069892
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):826-31
references.pmid: 15613486
references.citation: J Bacteriol. 2005 Nov;187(22):7716-26
references.pmid: 16267296
references.citation: J Biol Chem. 1999 Mar 26;274(13):8383-90
references.pmid: 10085069
references.citation: J Biol Chem. 2009 Jun 5;284(23):15867-79
references.pmid: 19346252
references.citation: Annu Rev Biochem. 1996;65:241-69
references.pmid: 8811180
references.citation: PLoS Comput Biol. 2007 Apr 6;3(4):e66
references.pmid: 17411337
references.citation: Mol Microbiol. 1993 Jan;7(1):7-19
references.pmid: 8382332
references.citation: J Cell Sci. 2001 Dec;114(Pt 24):4637-50
references.pmid: 11792828
references.citation: Science. 2005 Mar 18;307(5716):1746-52
references.pmid: 15705808
references.citation: J Am Chem Soc. 2009 Apr 8;131(13):4967-75
references.pmid: 19281244
references.citation: EMBO J. 1991 Jul;10(7):1699-709
references.pmid: 2050108
references.citation: Cell Microbiol. 2009 Feb;11(2):261-78
references.pmid: 19016782
references.citation: J Biol Chem. 1998 Jun 12;273(24):15030-4
references.pmid: 9614111
references.citation: Curr Opin Microbiol. 2009 Feb;12(1):67-73
references.pmid: 19157961
references.citation: J Lipid Res. 2006 Mar;47(3):467-75
references.pmid: 16401880
references.citation: Mol Cell. 2009 Dec 25;36(6):1060-72
references.pmid: 20064470
references.citation: Proc Natl Acad Sci U S A. 1989 Nov;86(21):8323-7
references.pmid: 2682646
references.citation: J Cell Biol. 1982 Apr;93(1):97-102
references.pmid: 7068762
references.citation: Nat Cell Biol. 2006 Sep;8(9):971-7
references.pmid: 16906144
references.citation: Annu Rev Genet. 1992;26:209-37
references.pmid: 1482112
references.citation: J Biol Chem. 2000 Apr 14;275(15):10796-801
references.pmid: 10753872
references.citation: Nature. 2007 Nov 15;450(7168):365-9
references.pmid: 17952054
references.citation: Infect Immun. 2010 Sep;78(9):3905-19
references.pmid: 20547746
references.citation: Nat Chem Biol. 2006 Nov;2(11):584-90
references.pmid: 17051234
references.citation: Science. 1998 Feb 6;279(5352):873-6
references.pmid: 9452389
references.citation: J Biol Chem. 2009 Feb 20;284(8):4846-56
references.pmid: 19095644
references.citation: Science. 1997 Mar 21;275(5307):1796-800
references.pmid: 9065405
references.citation: J Exp Med. 1983 Dec 1;158(6):2108-26
references.pmid: 6644240
references.citation: Science. 2006 Jul 21;313(5785):347-51
references.pmid: 16857939
references.citation: Cell. 2000 May 12;101(4):353-63
references.pmid: 10830163
references.citation: Trends Microbiol. 2007 Aug;15(8):372-80
references.pmid: 17632005
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12479-84
references.pmid: 15308774
references.citation: J Clin Microbiol. 1979 Oct;10(4):437-41
references.pmid: 393713
references.citation: Cell Microbiol. 2008 Dec;10(12):2416-33
references.pmid: 18673369
references.citation: Dev Cell. 2006 Jul;11(1):47-56
references.pmid: 16824952
references.citation: Infect Immun. 2006 Jun;74(6):3325-33
references.pmid: 16714560
references.citation: J Lipid Res. 2006 May;47(5):883-91
references.pmid: 16543601
references.citation: Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9607-11
references.pmid: 1409673
references.citation: PLoS Pathog. 2009 Jan;5(1):e1000278
references.pmid: 19165328
references.citation: J Biol Chem. 2005 Apr 15;280(15):14620-7
references.pmid: 15710609
references.citation: PLoS Pathog. 2009 Jul;5(7):e1000508
references.pmid: 19593377
references.citation: N Engl J Med. 1977 Dec 1;297(22):1189-97
references.pmid: 335244
references.citation: EMBO J. 1989 Apr;8(4):1093-8
references.pmid: 2663468
references.citation: Nat Cell Biol. 2002 Dec;4(12):945-54
references.pmid: 12447391
references.citation: Science. 2008 Jan 11;319(5860):210-3
references.pmid: 18187657
references.citation: Infect Immun. 1998 Sep;66(9):4450-60
references.pmid: 9712800
references.citation: Mol Microbiol. 1999 Jun;32(5):990-1001
references.pmid: 10361301
references.citation: N Engl J Med. 1977 Dec 1;297(22):1197-203
references.pmid: 335245
references.citation: J Biol Chem. 1997 May 30;272(22):14459-64
references.pmid: 9162087
references.citation: Cell Microbiol. 2009 Oct;11(10):1435-43
references.pmid: 19563462
references.citation: FEBS Lett. 1976 Dec 31;72(2):323-6
references.pmid: 16386050
references.citation: Science. 2002 Jan 25;295(5555):679-82
references.pmid: 11809974
references.citation: Nature. 1984 Aug 16-22;310(5978):583-6
references.pmid: 6087162
references.citation: J Exp Med. 2004 May 3;199(9):1201-11
references.pmid: 15117975
references.citation: Cell. 1997 Oct 17;91(2):253-62
references.pmid: 9346242
references.citation: Proc Natl Acad Sci U S A. 2010 May 11;107(19):8627-32
references.pmid: 20421494
references.citation: Cell. 1990 Oct 5;63(1):133-9
references.pmid: 2208277
references.citation: Infect Immun. 1995 Sep;63(9):3609-20
references.pmid: 7642298
references.citation: PLoS Pathog. 2006 Apr;2(4):e34
references.pmid: 16652170