Identification of a bacterial type III effector family with G protein mimicry functions.
Many bacterial pathogens use the type III secretion system to inject "effector" proteins into host cells. Here, we report the identification of a 24 member effector protein family found in pathogens including Salmonella, Shigella, and enteropathogenic E. coli. Members of this family subvert host cell function by mimicking the signaling properties of Ras-like GTPases. The effector IpgB2 stimulates cellular responses analogous to GTP-active RhoA, whereas IpgB1 and Map function as the active forms of Rac1 and Cdc42, respectively. These effectors do not bind guanine nucleotides or have sequences corresponding the conserved GTPase domain, suggesting that they are functional but not structural mimics. However, several of these effectors harbor intracellular targeting sequences that contribute to their signaling specificities. The activities of IpgB2, IpgB1, and Map are dependent on an invariant WxxxE motif found in numerous effectors leading to the speculation that they all function by a similar molecular mechanism.
Alto
Neal M
NM
Department of Pharmacology, Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Shao
Feng
F
Lazar
Cheri S
CS
Brost
Renee L
RL
Chua
Gordon
G
Mattoo
Seema
S
McMahon
Stephen A
SA
Ghosh
Partho
P
Hughes
Timothy R
TR
Boone
Charles
C
Dixon
Jack E
JE
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D004926:Escherichia coli / Q000145:classification / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D018716:Molecular Mimicry / Q000502:physiology*; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012485:Salmonella typhi / Q000502:physiology; D012763:Shigella flexneri / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D001426:Bacterial Proteins; D029701:Saccharomyces cerevisiae Proteins; D020928:Mitogen-Activated Protein Kinases; C508203:IpgB1 protein, Shigella flexneri; C508202:IpgB2 protein, Shigella flexneri; C051302:RHO1 protein, S cerevisiae; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins