PDBsum entry 6be0

Transferase

PDB id: 6be0

Contents

Protein chain

266 a.a.

Ligands

IHP

COA

Waters ×65

References listed in PDB file

Key reference

• Title: Structural analysis of the bacterial effector avra identifies a critical helix involved in substrate recognition.
• Authors: J.M.Labriola, Y.Zhou, B.Nagar.
• Ref.: Biochemistry, 2018, 57, 4985-4996. [DOI no: 10.1021/acs.biochem.8b00512]
• PubMed id: 30025209

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^ΔL140) abrogates the ability to suppress JNK signaling. Here, we present the first crystal structure of a bacterial effector from an animal pathogen, AvrA^ΔL140, 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^ΔL140 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.