Crystal structures of the CO and NO Bound DosS GAF-A domain and implications for DosS signaling in Mycobacterium tuberculosis

• Published in: Archives of biochemistry and biophysics 2016-12, Vol.612 (C), p.1-8
• Main Authors: Madrona, Yarrow, Waddling, Christopher A., Ortiz de Montellano, Paul R.
• Format: Article
• Language: English
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2016.10.005

DosS is a sensor in Mycobacterium tuberculosis that differentially responds to O 2 , NO, and CO, as well as to changes in the redox state of the prosthetic heme iron atom. The ferrous protein and its Fe(II)-NO and Fe(II)-CO complexes undergo autophosphorylation and subsequently transfer the phosphate group to DosR, a nuclear factor, to activate it. In contrast, autophosphorylation is negligible with the ferric protein and the Fe(II)-O 2 complex. To clarify the basis for this differential response to gases, we have determined the crystal structures of the NO- and CO-complexes of the DosS GAF-A domain, which contains the heme to which the gases bind. Comparison of these crystal structures with those reported for the phosphorylation-inactive ferric GAF-A domain suggest that the GAF-A domain is in a dynamic equilibrium between active and inactive states, and that the position of Glu87 in the heme cavity, which depends on the which gas is bound, acts as a modulator of the equilibrium, and therefore of catalytic activity.