title: Archaeal protoglobin structure indicates new ligand diffusion paths and modulation of haem-reactivity.
abstract: The structural adaptability of the globin fold has been highlighted by the recent discovery of the 2-on-2 haemoglobins, of neuroglobin and cytoglobin. Protoglobin from Methanosarcina acetivorans C2A-a strictly anaerobic methanogenic Archaea-is, to the best of our knowledge, the latest entry adding new variability and functional complexity to the haemoglobin (Hb) superfamily. Here, we report the 1.3 A crystal structure of oxygenated M. acetivorans protoglobin, together with the first insight into its ligand-binding properties. We show that, contrary to all known globins, protoglobin-specific loops and an amino-terminal extension completely bury the haem within the protein matrix. Access of O(2), CO and NO to the haem is granted by the protoglobin-specific apolar tunnels reaching the haem distal site from locations at the B/G and B/E helix interfaces. Functionally, M. acetivorans dimeric protoglobin shows a selectivity ratio for O(2)/CO binding to the haem that favours O(2) ligation and anticooperativity in ligand binding. Both properties are exceptional within the Hb superfamily.
authors.affiliation: Department of Biomolecular Sciences and Biotechnology, CNR-INFM, University of Milano, Via Celoria 26, Milano 20133, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Nardini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pesce
authors.forename: Liesbet
authors.initials: L
authors.lastname: Thijs
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Saito
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dewilde
authors.forename: Maqsudul
authors.initials: M
authors.lastname: Alam
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Coletta
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaccio
authors.forename: Luc
authors.initials: L
authors.lastname: Moens
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D018360:Crystallography, X-Ray; D004058:Diffusion; D006418:Heme / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D017020:Methanosarcina / Q000737:chemistry*; D008958:Models, Molecular; D010100:Oxygen / Q000378:metabolism; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D019843:Archaeal Proteins; D008024:Ligands; D006418:Heme; D002248:Carbon Monoxide; D010100:Oxygen