Human brain neuroglobin structure reveals a distinct mode of controlling oxygen affinity.
Neuroglobin, mainly expressed in vertebrate brain and retina, is a recently identified member of the globin superfamily. Augmenting O(2) supply, neuroglobin promotes survival of neurons upon hypoxic injury, potentially limiting brain damage. In the absence of exogenous ligands, neuroglobin displays a hexacoordinated heme. O(2) and CO bind to the heme iron, displacing the endogenous HisE7 heme distal ligand. Hexacoordinated human neuroglobin displays a classical globin fold adapted to host the reversible bis-histidyl heme complex and an elongated protein matrix cavity, held to facilitate O(2) diffusion to the heme. The neuroglobin structure suggests that the classical globin fold is endowed with striking adaptability, indicating that hemoglobin and myoglobin are just two examples within a wide and functionally diversified protein homology superfamily.
Pesce
Alessandra
A
Department of Physics-INFM and Centre for Excellence in Biomedical Research, University of Genova, Via Dodecaneso 33, I-16146 Genova, Italy.
Dewilde
Sylvia
S
Nardini
Marco
M
Moens
Luc
L
Ascenzi
Paolo
P
Hankeln
Thomas
T
Burmester
Thorsten
T
Bolognesi
Martino
M
D000595:Amino Acid Sequence; D001923:Brain Chemistry; D005914:Globins / Q000737:chemistry*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D000078787:Neuroglobin; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins; D010100:Oxygen