Structure and Proposed Activity of a Member of the VapBC Family of Toxin-Antitoxin Systems

Abstract

In prokaryotes, cognate toxin-antitoxin pairs have long been known, but no three-dimensional structure has been available for any given complex from Mycobacterium tuberculosis. Here we report the crystal structure and activity of a member of the VapBC family of complexes from M. tuberculosis. The toxin VapC-5 is a compact, 150 residues, two domain α/β protein. Bent around the toxin is the VapB-5 antitoxin, a 33-residue α-helix. Assays suggest that the toxin is an Mg-enabled endori-bonuclease, inhibited by the antitoxin. The lack of DNase activity is consistent with earlier suggestions that the complex represses its own operon. Furthermore, analysis of the interactions in the binding of the antitoxin to the toxin suggest that exquisite control is required to protect the bacteria cell from toxic VapC-5. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.