title: Functional Role of the C-Terminal Amphipathic Helix 8 of Olfactory Receptors and Other G Protein-Coupled Receptors.
abstract: G protein-coupled receptors (GPCRs) transduce various extracellular signals, such as neurotransmitters, hormones, light, and odorous chemicals, into intracellular signals via G protein activation during neurological, cardiovascular, sensory and reproductive signaling. Common and unique features of interactions between GPCRs and specific G proteins are important for structure-based design of drugs in order to treat GPCR-related diseases. Atomic resolution structures of GPCR complexes with G proteins have revealed shared and extensive interactions between the conserved DRY motif and other residues in transmembrane domains 3 (TM3), 5 and 6, and the target G protein C-terminal region. However, the initial interactions formed between GPCRs and their specific G proteins remain unclear. Alanine scanning mutagenesis of the murine olfactory receptor S6 (mOR-S6) indicated that the N-terminal acidic residue of helix 8 ofmOR-S6 is responsible for initial transient and specific interactions with chimeric Gα15_olf, resulting in a response that is 2.2-fold more rapid and 1.7-fold more robust than the interaction with Gα15. Our mutagenesis analysis indicates that the hydrophobic core buried between helix 8 and TM1-2 ofmOR-S6 is important for the activation of both Gα15_olfand Gα15. This review focuses on the functional role of the C-terminal amphipathic helix 8 based on several recent GPCR studies.
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorioka, Ikeda, Osaka 563-8577, Japan. taka-sato@aist.go.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorioka, Ikeda, Osaka 563-8577, Japan. takashi-kawasaki@aist.go.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorioka, Ikeda, Osaka 563-8577, Japan. s-mine@aist.go.jp.
authors.forename: Shouhei
authors.initials: S
authors.lastname: Mine
authors.affiliation: College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan. h-matsu@fc.ritsumei.ac.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Matsumura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D018035:Receptors, Odorant / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D018035:Receptors, Odorant; C112631:G protein alpha 16; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: Ca2+ imaging; G protein-coupled receptor; activation; homology model; interaction; olfactory receptor; response kinetics