title: A globin domain in a neuronal transmembrane receptor of Caenorhabditis elegans and Ascaris suum: molecular modeling and functional properties.
abstract: We report the structural and biochemical characterization of GLB-33, a putative neuropeptide receptor that is exclusively expressed in the nervous system of the nematode Caenorhabditis elegans. This unique chimeric protein is composed of a 7-transmembrane domain (7TM), GLB-33 7TM, typical of a G-protein-coupled receptor, and of a globin domain (GD), GLB-33 GD. Comprehensive sequence similarity searches in the genome of the parasitic nematode, Ascaris suum, revealed a chimeric protein that is similar to a Phe-Met-Arg-Phe-amide neuropeptide receptor. The three-dimensional structures of the separate domains of both species and of the full-length proteins were modeled. The 7TM domains of both proteins appeared very similar, but the globin domain of the A. suum receptor surprisingly seemed to lack several helices, suggesting a novel truncated globin fold. The globin domain of C. elegans GLB-33, however, was very similar to a genuine myoglobin-type molecule. Spectroscopic analysis of the recombinant GLB-33 GD showed that the heme is pentacoordinate when ferrous and in the hydroxide-ligated form when ferric, even at neutral pH. Flash-photolysis experiments showed overall fast biphasic CO rebinding kinetics. In its ferrous deoxy form, GLB-33 GD is capable of reversibly binding O2 with a very high affinity and of reducing nitrite to nitric oxide faster than other globins. Collectively, these properties suggest that the globin domain of GLB-33 may serve as a highly sensitive oxygen sensor and/or as a nitrite reductase. Both properties are potentially able to modulate the neuropeptide sensitivity of the neuronal transmembrane receptor.
authors: From the Departments of Biomedical Sciences and.
authors: Lesley
authors: L
authors: Tilleman
authors: From the Departments of Biomedical Sciences and.
authors: Francesca
authors: F
authors: Germani
authors: the Department of Biology, Ghent University, 9000 Ghent, Belgium.
authors: Sasha
authors: S
authors: De Henau
authors: the Department of Bioscience, Aarhus University, 8000 Aarhus, Denmark.
authors: Signe
authors: S
authors: Helbo
authors: Physics, University of Antwerp, 2610 Antwerp, Belgium.
authors: Filip
authors: F
authors: Desmet
authors: From the Departments of Biomedical Sciences and.
authors: Herald
authors: H
authors: Berghmans
authors: Physics, University of Antwerp, 2610 Antwerp, Belgium.
authors: Sabine
authors: S
authors: Van Doorslaer
authors: the Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, 8006 Zürich, Switzerland, Institute of Physiology, University of Duisburg-Essen, D-45147 Essen, Germany, and.
authors: David
authors: D
authors: Hoogewijs
authors: the Functional Genomics and Proteomics Group, KU Leuven, 3000 Leuven, Belgium.
authors: Liliane
authors: L
authors: Schoofs
authors: the Department of Biology, Ghent University, 9000 Ghent, Belgium.
authors: Bart P
authors: BP
authors: Braeckman
authors: From the Departments of Biomedical Sciences and.
authors: Luc
authors: L
authors: Moens
authors: the Department of Bioscience, Aarhus University, 8000 Aarhus, Denmark.
authors: Angela
authors: A
authors: Fago
authors: From the Departments of Biomedical Sciences and sylvia.dewilde@uantwerpen.be.
authors: Sylvia
authors: S
authors: Dewilde
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017165:Ascaris suum / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005914:Globins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009572:Nitrite Reductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018013:Receptors, Neuropeptide / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; D009211:Myoglobin; D018013:Receptors, Neuropeptide; D011994:Recombinant Proteins; D006418:Heme; D005914:Globins; D007501:Iron; D009572:Nitrite Reductases; D010100:Oxygen
keywords: Electron Paramagnetic Resonance (EPR); Hemoglobin; Kinetics; Oxygen Binding; Redox Signaling