The C-Terminal Domain of the Virulence Factor mgtc Is a Divergent ACT Domain

Abstract

MgtC is a virulence factor of unknown function important for survival insidemacrophages in several intracellular bacterial pathogens, includingMycobacterium tuberculosis. It is also involved in adaptation toMg2+ deprivation, but previous work sug-gested thatMgtC is not aMg2+ transporter. In this study, we demonstrated that the amount of theM. tuberculosisMgtC protein is not signicantly increased byMg2+ deprivation. Members of theMgtC protein family share a conservedmembrane N-termi-nal domain and amore divergent cytoplasmic C-terminal domain. To get insights intoMgtC functional and structural organiza-tion, we have determined the nuclearmagnetic resonance (NMR) structure of the C-terminal domain ofM. tuberculosisMgtC. This structure is not affected by theMg2+ concentration, indicating that it does not bindMg2+. The structure of the C-terminal domain forms a βαββαβ fold found in smallmolecule binding domains called ACT domains. However, theM. tuberculosis MgtC ACT domain differs fromcanonical ACT domains because it appears to lack the ability to dimerize and to bind smallmol-ecules. We have shown, using a bacterial two-hybrid system, that theM. tuberculosisMgtC protein can dimerize and that the C-terminal domain somehow facilitates this dimerization. Taken together, these results indicate thatM. tuberculosisMgtC does not have an intrinsic function related toMg2+ uptake or binding but could act as a regulatory factor based on protein-protein interaction that could be facilitated by its ACT domain. © 2012, American Society for Microbiology.