Bacterial effectors and their motifs


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Bacterial Effector Proteins and their domains/motifs

Many bacterial pathogens that cause some of the world’s most devastating diseases deliver proteins (called effectors) into the cells of their host - which is a requirement to cause disease.

Over 400 predicted or proven effectors from a wide range of bacterial species have been identified that are delivered by dedicated type three secretion systems ( TTSS / T3SS). Many effector proteins are unique with little sequence similarity to any other known proteins, while others make up large effectors families. Almost all bacterial pathogens possess at least one effector that has a homologue or chimera in another bacterial species.

Below is a Table of bacterial effector proteins that have been proven to be secreted from many important bacterial pathogens.


Useful Effector Links

ModLab -Effector protein predictor

Effective- Effector predictor

	T3SEdb - effector database

		T3SEdb - effector predictor

		SIEVE - effector predictor

	Proven Effector repertoire	Papers on effector repertoires
Salmonella species	AvrA, PipB, PipB2, SifA, SipA, SipB, SipC, SopA, SopB/SigD, SopD, SopD2, SopE, SopE2, SpiC, SptP, SpvB, SpvC, SseF, SseG, SseJ, SseL, SspH1, SteC, SteB, SteA, SspH2, SlrP	Waterman and Holden (2005), McGhie et al (2009), Schlumberger and Hardt (2006)
E.coli and Citrobacter	EspB, EspF, EspG, EspG2/Orf3, Tir, EspH, EspZ, NleA, NleB, NleC, NleD, NleE, NleF, NleG, NleH, EspM, EspX, EspY, EspJ, EspK, EspL, EspO,	Dean and Kenny (2009), Tobe et al (2006), Deng et al (2004)
Shigella species.	IpaB, IpaC, IpaD, IpaA, IpaJ, IpgD, IpgB1, IpgB2, IcsB, OspC2, OspC3, OspD1, OspZ, OspD2, OspB, OspC1, OspF, VirA, OspD3, OspE1, OspE2, OspG, IpaH9.8, IpaH7.8, IpaH1.4, IpaH4.5, IpaH2.5, IpaH3	Schroeder and Hilbi (2008), Parsot (2009)
Yersinia species	YopM, YopT, YopP/J, YopE, YopH, YpkA/YopO and from Yersinia enterocolitica Biovar 1B YspA, YspL, YspP, YspF, YspE, YspI, YspK, YspM	Matsumoto and Young (2009), Shao (2008)
Ralstonia species	GALA1-7, SKWP1-6, HLK1-3, RipB, PopW, PopC, AvrA, PopB, PopA, RipA, AWR1-6, PopP2, SKWP7 (many others predicted)	Poueymiro and Genin (2009)
Pseudomonas syringae	AvrB, AvrBs3, AvrPphB, AvrPto, AvrPtoB, AvrRpm1, AvrRpt2, AvrXa27, AvrXv4, GALA, HopAI1, HopAO1, HopI1, HopM1, HopU1, HsvB, HsvG, PthXo1, PthXo6/7, XopD, AvrPphE, AvrPphF, HopP1, HopZ (many others predicted)	Cunnac et al (2009) Grant et al (2006) Lindeberg et al (2005)
Xanthomonas species	AvrBs1, AvrBs2, AvrBs3, Avrb6, AvrXa7, PthA, AvRxo1, AvRxv, AvrBsT, AvrXv4, XopJ, AvrXccC, AvrXv3, XopX, HpaA, XopB. XopC, XopD, XopE1, XopE2, XopF1, XopF2, XopN, XopO, XopP, XopQ	Kay and Bonas (2009) Gurlebeck et al (2005) Grant et al (2006)
Pseudomonas aeruginosa	ExoS, ExoT, ExoU, ExoY	Engel and Balachandran (2009)
Chlamydia species	Tarp, IncA, CT847, CADD,	Valdivia (2008) Betts et al (2009)

Bacterial Effector FUNCTIONS and MOTIFS

The functional repertoire of bacterial effector proteins is quite remarkable (see picture of the host cell below). To orchestrate such subversive functions, effector proteins often encode small motifs that function inside the eukaryotic cell. These domains and motifs are also given in the table below


	Bacterial Effector functions (Dean 2011; FEMS Microbiol Rev)


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	Bacterial Effector motifs (Dean 2011; FEMS Microbiol Rev)


	Effector motif characteristics (Dean 2011; FEMS Microbiol Rev)

Subcellular target/activity	Effectors	Description of responsible motifs
Intracellular membrane	PipP2, SopD2, YopE, ExoS	LFNEF (PipP2), WEK(I/M)xxFF (SopD2); N-terminal Lx₂Rx₄L (YopE, ExoS); CLCCFL prenylation motif (SifA)
Nucleus (NLS)	PopB, PopP2, XopD, AvrBs3	Bipartite NLS: KRKR and KKKKKR (PopB); RRRR and RRQRQ (PopP2). Monopartite NLS: XopD, TAL effectors such as AvrBs3 E.g. KRPR
Nucleolus	EspF	Atypical nuclear/nucleolar targeting motif
Plasma membrane	ExoU, HopZ, AvrPto, AvrPphB	C-terminal MLD containing an essential KAWRN motif (ExoU); PM targeting mediated by Myr and Palm motifs (several plant pathogen effectors)
Mitochondrial MTS	Map, EspF, SopA	N-terminal domain rich in arginine and leucine (Map and EspF); a critical Leu16 (EspF); internal atypical domain (SopA)
Golgi	STE motif, SseG	WEK(I/M)xxFF motif alone; Internal golgi targeting domain (SseG)

Ser/Thr kinase	YpkA	Large domain similar to Ser/Thr kinases with critical Asp287 and Lys269 residues
RhoGAP	AexT, ExoS, ExoT, YopE, SptP	Critical arginine finger motif GxLRx₃T and an essential downstream loop conatianing the consensus QWGTxGG (AexT, ExoS, ExoT, YopE, SptP); Tir also possesses the arginine finger GxLR
RhoGEF	SopE, SopE2, BopE	Catalytic loop containing the GAGA motif
RhoGEF (WxxxE family)	Map, SifA, EspM2	Catalytic loop containing the consensus (D/P/E)x₃AQ; a conserved WxxxE structural motif
Lipase	SseJ	C-terminal domain with a GDSL lipase motif and a SHD catalytic triad
Phospholipase	ExoU	Large cPLA₂ domain. SD catalytic dyad of - GxSx(G/S) hydrolase motif and a Dx(G/A) active site motif. An essential GGGxxG motif.
Cysteine protease	YopJ, YopT, AvrPphB	Catalytic HEC triad: HX₁₈EX₄₄C (YopJ); catalytic CHD triad (YopT, AvrPphB) and N-terminal Rho binding domain (YopT), autoproteolytic site GDKG (AvrPphB)
E3 Ub ligase	SopA, IpaH, SspH1	Active site HECT motif - Lx₄TC (SopA); CxD motif (IpaH and SspH1)
ADP-ribosyltransferas e	HopU1, SpvB, ExoS, ExoT	ADPRT conserved region I - invariant arginine; region II - Gx₉ST(S/T); region III – NAD binding ExE motif
Kinase	SteC, YpkA, OspG	Kinase subdomain I: nucleotide positioning motif - GxGxxG (SteC); subdomain II: invariant lysine residue; subdomain III: invariant glutamic acid
Protein Phosphatase	YopH, SptP	PTPase motif - HC(x)₅R(S/T); essential WPD loop
PIP phosphatase	IpgD, SopB	PIPase domain - FN(F/V)G(V/I)NE (motif 1) and CKSxKDRTxM (motif 2)
pY motifs	Tir	Src kinase phosphorylation motif - ExLYxx(I/V)
F boxes	GALA family	The LPx₆I type F box (all GALA effectors)
Lyase	OspF, SpvC HopAI1	Lyase motif - GDKxH – essential for lyase activity
WH2	VopL, VopF,	Homology to WASP WH2; contains the LKKV-like motif.
D motif	SpvC, OspF	Docking motif required for specific binding to MAPKs
FH1	VopF	Highly homologous to mammalian formins (VopF)
Actin-related protein binding	IpaA, Tir, EspF	Phosphotyrosine Nck binding YDEV motif (Tir), vinculin binding domain (IpaA), N-WASP binding motif (EspF),
14-3-3 binding site	ExoS	Mediates binding to the 14-3-3 protein FAS to activate the ADPRT domain
SH3 binding motif	EspF	Repeated motif; binds sorting nexin 9 via a conserved RxAPxxP motif
J domain	HopI1	Hsp70 interaction domain with an invariant HPD motif
PDZ1 binding motif	Map, NleA, NleH1	Extreme C-terminal motif: -SKI (NleH1), -TRL (Map), -TRV (NleA); mediates effector sorting and protein-protein interaction
Transcription activation domain	AvrBs3 effector family	Far C-terminal region of the TAL effectors. Functions in conjunction with the central DNA binding repeat region
Caspase-3 site	SipA, SopA	Processing site containing the motif DEVD
Fic domain	VopS	Required for AMPylation of Rho GTPases. C-terminal motif :HxFx(D/E)GNGR


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	Effector motifs with noted roles in virulence (Dean 2011; FEMS Microbiol Rev)

Bacterial Effector	Domain or motif with a virulence role	Reference
SipA	DEVD- Caspase 3 cleavage site	(Srikanth et al., 2010)
SseI	Cys178 – unknown function	(McLaughlin et al., 2009)
SseL	Cysteine protease site	(Rytkonen et al., 2007)
YopM	Leucine Rich Repeats (6-15)	(McPhee et al., 2010)
ExoS	ADP ribosyltransferase domain	(Shaver and Hauser, 2004)
HopF2Pto	Myristoylation motif	(Wilton et al., 2010)
AvrPto	Ser149 phosphorylation	(Anderson et al., 2006)
WtsE and AvrE1	WxxxE motif	(Ham et al., 2009)
SifA	CAAX box	(Boucrot et al., 2003)
GALA effectors	F-box	(Angot et al., 2006)
SseJ	Lipase domain - SHD triad	(Ohlson et al., 2005)
SpvB	ADP ribosyltransferase domain	(Lesnick et al., 2001)
NleA	PDZ domain	(Lee et al., 2008)
YpkA	Kinase domain	(Wiley et al., 2006)
YopE	GAP domain	(Black and Bliska, 2000)


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