How a DNA mimic catches and cleaves NF-κB

Abstract

Bacterial pathogens use several strategies to infect host cells, one of which involves blocking host defenses. During infection, the bacterial effector proteins GtgA, GogA, PipA, and NleC are injected into host cells by the type III secretion system (T3SS), where they suppress the proinflammatory NF-κB signaling pathway to dampen immune responses. The authors demonstrate that these effectors bind NF-κB via their DNA-mimicking regions and uncover differences in effector sequences and structures explaining the individual specificities of these effectors for distinct NF-κB subunits.

Figure 1.

Cleavage of NF-κB subunits by bacterial T3SS zinc metalloprotease effector proteins. GtgA and NleC (represented in the cartoon with the zinc ion as a green sphere, water as a red sphere, and zinc binding and catalytic glutamate residues as sticks) have been shown to cleave p65 (depicted as surface structures with the NTD in green and the DD in cyan) at the peptide bond before Arg-41 (blue) and Glu-39 (red), respectively. This cleavage releases a short peptide (light purple) from the p65 N terminus, which previously threaded through the center of the p65 structure, and thereby disrupts it, preventing DNA binding.