Cryo-EM structure of Vibrio cholerae aldehyde-alcohol dehydrogenase spirosomes

Aldehyde-alcohol dehydrogenase (AdhE) is a metabolic enzyme and virulence factor in bacteria. E. coli. AdhE (eAdhE) multimerizes into spirosomes that are essential for enzymatic activity. However, it is unknown whether AdhE structure is conserved in divergent bacteria. Here, we present the cryo-EM structure of AdhE (vAdhE) from Vibrio cholerae to 4.31 angstrom resolution. Overall, vAdhE spirosomes are similar to eAdhE with conserved subunit arrangement. However, divergences in key oligomerization residues cause vAdhE to form labile spirosomes with lower enzymatic activity. Mutating the vAdhE oligomerization interface to mimic eAdhE increases spirosome stability and enzymatic activity to levels comparable to eAdhE. These results support the generality of AdhE spirosome structures, and provide a structural basis to target vAdhE to attenuate bacterial virulence. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

This study presents the cryo-EM structure of AdhE from Vibrio cholerae, revealing similarities and differences with AdhE from Escherichia coli. Divergences in key oligomerization residues in vAdhE lead to unstable spirosomes and lower enzymatic activity, which can be improved by mutating the oligomerization interface to mimic eAdhE. These results support the generality of AdhE spirosome structures and provide insights for targeting vAdhE to attenuate bacterial virulence.