6BE0

AvrA delL154 with IP6, CoA

Summary for 6BE0

• Entry DOI: 10.2210/pdb6be0/pdb
• Descriptor: AvrA, INOSITOL HEXAKISPHOSPHATE, COENZYME A, ... (4 entities in total)
• Functional Keywords: acetyltransferase, yopj family, ip6, bacterial effector, transferase
• Biological source: Salmonella typhimurium (strain 4/74)
• Total number of polymer chains: 1
• Total formula weight: 35239.37

Authors

Labriola, J.M.,Nagar, B. (deposition date: 2017-10-24, release date: 2018-08-01, Last modification date: 2023-10-04)

Primary citation

Labriola, J.M.,Zhou, Y.,Nagar, B.
Structural Analysis of the Bacterial Effector AvrA Identifies a Critical Helix Involved in Substrate Recognition.
Biochemistry, 57:4985-4996, 2018

PubMed 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 (AvrA) abrogates the ability to suppress JNK signaling. Here, we present the first crystal structure of a bacterial effector from an animal pathogen, AvrA, 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 AvrA 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.

PubMed: 30025209
DOI: 10.1021/acs.biochem.8b00512

Experimental method

X-RAY DIFFRACTION (2.438 Å)