The T3SS is a syringe-like multi-protein complex which spans both the inner and outer bacterial membranes and the host cell membrane. It allows various Gram-negative bacteria to inject a set of specific proteins, known as effectors, directly into the cytoplasm of the host cell. These effectors then act to alter host signalling pathways to the advantage of the pathogen, often mimicking eukaryote-specific activities. There are more than a hundred known families of confirmed and potential effectors secreted by the T3SS. One of the main targets for effector proteins is the host ubiquitin proteasome system (UPS). Bacteria lack this system but they secrete many effectors with UPS-specific functions, with those able to mimic the E3 ubiquitin ligase activity being the most abundant and diverse group.

The T3SS of pathogenic E. coli, was thought to be strictly encoded within a specific locus in its genome named the "locus of enterocyte effacement" or LEE. However, later studies revealed a large number of additional non-LEE-encoded (Nle) effector proteins. Structural domains comprising this superfamily share the structure of the effector protein NleG, the largest family among these newly identified effectors with fourteen members in the enterohaemorrhagic (EHEC) O157:H7 strain alone. NleG effectors are E3 ubiquitin ligases analogous to RING finger and U-box enzymes in eukaryotes PMID:20585566.