The crystal structure of wild-type human brain neuroglobin reveals flexibility of the disulfide bond that regulates oxygen affinity.
Neuroglobin plays an important function in the supply of oxygen in nervous tissues. In human neuroglobin, a cysteine at position 46 in the loop connecting the C and D helices of the globin fold is presumed to form an intramolecular disulfide bond with Cys55. Rupture of this disulfide bridge stabilizes bi-histidyl haem hexacoordination, causing an overall decrease in the affinity for oxygen. Here, the first X-ray structure of wild-type human neuroglobin is reported at 1.74 Å resolution. This structure provides a direct observation of two distinct conformations of the CD region containing the intramolecular disulfide link and highlights internal cavities that could be involved in ligand migration and/or are necessary to enable the conformational transition between the low and high oxygen-affinity states following S-S bond formation.
Synchrotron SOLEIL, L'Orme des Merisiers, Saint-Aubin, 91190 Gif-sur-Yvette, France.
Beatriz G
BG
Guimarães
Laboratoire d'Enzymologie et Biochimie Structurales, Centre de Recherche de Gif, CNRS, 1 Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
Djemel
D
Hamdane
Inserm U779, Université Paris XI, 78 Rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France.
Christophe
C
Lechauve
Inserm U779, Université Paris XI, 78 Rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France.
Michael C
MC
Marden
Laboratoire d'Enzymologie et Biochimie Structurales, Centre de Recherche de Gif, CNRS, 1 Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
Béatrice
B
Golinelli-Pimpaneau
D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D005914:Globins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D000078787:Neuroglobin; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
D004220:Disulfides; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins; D010100:Oxygen
disulfide bonds; globins; neuroglobin; oxygen homeostasis; regulatory switch