title: Identification of residues in human neuroglobin crucial for Guanine nucleotide dissociation inhibitor activity.
abstract: Neuroglobin (Ngb) is a recently discovered vertebrate heme protein that is expressed in the brain and can reversibly bind oxygen. We previously demonstrated that ferric human Ngb binds to the alpha-subunits of heterotrimeric G proteins (Galpha) and acts as a guanine nucleotide dissociation inhibitor (GDI) for Galpha. Here we have investigated the interaction between Ngb and Galpha in more detail. We report that zebrafish Ngb, which shares about 50% amino acid sequence identity with human Ngb, does not have a GDI activity for Galpha. By carrying out exon swapping between zebrafish and human Ngb and site-directed mutagenesis, we have identified several residues that are crucial for the GDI activity of human Ngb.
authors.affiliation: Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan. kei@wakasugi.mbox.media.kyoto-u.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Wakasugi
authors.forename: Isao
authors.initials: I
authors.lastname: Morishima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D005914:Globins / Q000737:chemistry* / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism; D006454:Hemoglobins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D000078787:Neuroglobin; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D020730:Guanine Nucleotide Dissociation Inhibitors; D006150:Guanine Nucleotides; D006454:Hemoglobins; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D029961:Zebrafish Proteins; D005914:Globins; D020962:Heterotrimeric GTP-Binding Proteins