Crystal structure of archeal protoglobin: Novel ligand diffusion paths to the heme

The protein structural adaptability of the globin fold has been highlighted by the recent discovery of 2-on-2 hemoglobins, of neuroglobin, cytoglobin, and the characterization of their three-dimensional structures. Protoglobin from Methanosarcina acetivorans C2A is the latest entry in the hemoglobin superfamily, adding to it new structural variability and functional complexity. The 1.3˚A crystal structure of oxygenated M. acetivorans protoglobin shows that, contrary to all known globins, protoglobin-specific loops and a N-terminal extension completely bury the heme within the protein matrix. Access of diatomic ligands (such as O2, CO, and NO) to the heme is however granted by protoglobin-specific apolar tunnels that reach the heme distal site from entry sites at the B/G and B/E helix interfaces. Functionally, M. acetivorans dimeric protoglobin displays a selectivity ratio for O2/CO binding to the heme that favours O2 ligation, a property that is exceptional within the hemoglobin superfamily