MADP-RTs: versatile virulence factors from bacterial pathogens of plants and mammals

Lennart Wirthmueller,Mark J Banfield

doi:10.3389/fpls.2012.00142

Abstract

Mono ADP-ribosyltransferases (mADP-RTs) are a family of enzymes that cleave NAD+ and covalently attach the ADP-ribosyl moiety to target proteins. mADP-RTs are well established as important virulence factors of bacteria that infect mammals. Cholera toxin, pertussis toxin, and diphtheria toxin are three of the best-known examples of mADP-RTs. They modify host target proteins in order to promote infection and/or killing of the host cell. Despite low sequence similarity at the primary amino acid level, mADP-RTs share a conserved core catalytic fold and structural biology has made important contributions to elucidating how mADP-RTs modify mammalian host targets. Recently, mADP-RTs were shown to be present in plant pathogenic bacteria, suggesting that mADP-RTs are also important virulence factors of plant pathogens. Crystal structures of plant pathogenic bacterial mADP-RTs are also now available. Here we review the structure/function of mADP-RTs from pathogens of mammals and plants, highlighting both commonalities and differences.

Highlights

Mono ADP-ribosyltransferases are a family of enzymes that cleave NAD+ and covalently attach the ADP-ribosyl moiety to target proteins. mADP-RTs are well established as important virulence factors of bacteria that infect mammals
The manipulating activities of mADP-RTs often culminate in killing the infected host cell and many pathogen secreted mADP-RTs are referred to as toxins (Holbourn et al, 2006)
Some mADP-RTs from Gram-negative bacteria rely on host cell delivery by the bacterial type three secretion system (T3SS) and consist only of the catalytic domain preceded by a type three secretion signal and host cell targeting domains (Deng and Barbieri, 2008)

Summary

Introduction

Mono ADP-ribosyltransferases (mADP-RTs) are a family of enzymes that cleave NAD+ and covalently attach the ADP-ribosyl moiety to target proteins. mADP-RTs are well established as important virulence factors of bacteria that infect mammals. Most mADP-RTs retain three structurally conserved features (Holbourn et al, 2006): (1) The arom-H/R motif is composed of an aromatic amino acid followed by His or Arg. This motif either contributes to NAD+ binding or supports the structural integrity of the NAD+ binding site; (2) The ARTT loop contains the conserved catalytic Glu residue required for NAD+ cleavage and transferase activity.

Results

Conclusion