NMR structure of a human homologous methuselah gene receptor peptide.
Human APG1 gene is homologous to Drosophila methuselah gene associated with extended life span. A peptide (APG1: RNGKRSNRTLREE) corresponding to a predicted region of the intracellular third loop of G protein-coupled receptor coded in human APG1 gene could activate Gi protein alpha subunit directly. The three-dimensional molecular structure of the peptide in SDS-d25 micelles was determined by 2D 1H NMR spectroscopy. APG1 formed an alpha-helical structure at the C-terminal site and a positive charge cluster at the N-terminal site. The cluster was also found in several other Gi protein-coupled receptor peptides. Therefore, the positive charge cluster on the helical structure might be engaged in G protein activation.
Kikkou
Tatsuhiko
T
Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba 288-0025, Japan.
Matsumoto
Osamu
O
Ohkubo
Tadayasu
T
Kobayashi
Yuji
Y
Tsujimoto
Gozoh
G
D000595:Amino Acid Sequence; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
C516583:APG1 peptide, human; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019206:GTP-Binding Protein alpha Subunits, Gi-Go