Structural Analysis of the Bacterial Effector AvrA Identifies a Critical Helix Involved in Substrate Recognition
Abstract
Bacterial effector proteins are essential for the infection and proliferation of pathogenic bacteria through manipulation of host immune response pathways. AvrA is a Salmonella effector that belongs to the YopJ family of acetyltransferases, which suppresses c-JUN N-terminal kinase (JNK) signaling in mammals through acetylation of mitogen-activated receptor kinase kinases 4 and 7 (MKK4/7). Interestingly, there are two paralogues of AvrA that differ by only a single internal leucine residue, which when absent (AvrAΔL140) abrogates the ability to suppress JNK signaling. Here, we present the first crystal structure of a bacterial effector from an animal pathogen, AvrAΔL140, accompanied by a thorough biophysical characterization of both AvrA variants. The structure in complex with inositol hexaphosphate and coenzyme A reveals two closely associated domains consisting of a catalytic core that resembles the CE clan peptidases and a wedge-shaped regulatory region that mediates cofactor and substrate binding. The loss of the putative function of AvrAΔL140 is due to its inability to interact with MKK4/7, which ultimately arises from an altered conformation of a critical helix adjacent to the active site that harbors L140. These results p...Continue Reading
References
A newly discovered post-translational modification--the acetylation of serine and threonine residues
Structure of a pathogen effector reveals the enzymatic mechanism of a novel acetyltransferase family
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