Structural highlights
FunctionPublication Abstract from PubMedBacterial effector proteins are essential for the infection and proliferation of pathogenic bacteria through manipulation of host immune response pathways. AvrA is a Salmonella effector belonging to the YopJ family of acetyltransferases, which suppresses c-JUN N-terminal kinase (JNK) signaling in mammals through acetylation of mitogen activated receptor kinase kinase 4/7 (MKK4/7). Interestingly, two paralogues of AvrA exist that differ by only a single internal leucine residue, which when absent (AvrAL140), abrogates the ability to suppress JNK signaling. Here, we present the first crystal structure of a bacterial effector from an animal pathogen, AvrAL140, 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 co-factor and substrate binding. The loss of the putative function of AvrAL140 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 provide general insights into substrate recognition across the YopJ family of acetyltransferases. Structural analysis of the bacterial effector, AvrA, identifies a critical helix involved in MKK4-substrate recognition.,Labriola J, Zhou Y, Nagar B Biochemistry. 2018 Jul 19. doi: 10.1021/acs.biochem.8b00512. PMID:30025209[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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