title: A GAF domain in the hypoxia/NO-inducible Mycobacterium tuberculosis DosS protein binds haem.
abstract: The majority of the Mycobacterium tuberculosis response to hypoxia and nitric oxide is through the DosRS (DevRS) two-component regulatory system. The N-terminal input domain of the DosS sensor contains two GAF domains. We demonstrate here that the proximal GAF domain binds haem, and identified histidine 149 of DosS as critical to haem-binding; the location of this histidine residue is similar to the cGMP-binding site in a crystal structure of cyclic nucleotide phosphodiesterase 2A. GAF domains are frequently involved in binding cyclic nucleotides, but this is the first GAF domain to be identified that binds haem. In contrast, PAS domains (similar to GAF domains in structure but not primary sequence) frequently use haem cofactors, and these findings further illustrate how the functions of these domains overlap. We propose that the activation of the DosS sensor is controlled through the haem binding of molecular oxygen or nitric oxide.
authors.affiliation: Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Sunita
authors.initials: S
authors.lastname: Sardiwal
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Kendall
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Movahedzadeh
authors.forename: Stuart C G
authors.initials: SC
authors.lastname: Rison
authors.forename: Neil G
authors.initials: NG
authors.lastname: Stoker
authors.forename: Snezana
authors.initials: S
authors.lastname: Djordjevic
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D003001:Cloning, Molecular; D006418:Heme / Q000378:metabolism*; D006639:Histidine; D000860:Hypoxia; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D006656:Protamine Kinase / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D009569:Nitric Oxide; D006418:Heme; D006639:Histidine; C506260:DevS protein, Mycobacterium tuberculosis; D006656:Protamine Kinase; D010100:Oxygen