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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)

Bacterial effector functions -Salmonella Shigella etc

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Bacterial Effector motifs (Dean 2011; FEMS Microbiol Rev)

Effector motifs

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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