title: Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors.
abstract: Insect odorant receptors (ORs) comprise an enormous protein family that translates environmental chemical signals into neuronal electrical activity. These heptahelical receptors are proposed to function as ligand-gated ion channels and/or to act metabotropically as G protein-coupled receptors (GPCRs). Resolving their signalling mechanism has been hampered by the lack of tertiary structural information and primary sequence similarity to other proteins. We use amino acid evolutionary covariation across these ORs to define restraints on structural proximity of residue pairs, which permit de novo generation of three-dimensional models. The validity of our analysis is supported by the location of functionally important residues in highly constrained regions of the protein. Importantly, insect OR models exhibit a distinct transmembrane domain packing arrangement to that of canonical GPCRs, establishing the structural unrelatedness of these receptor families. The evolutionary couplings and models predict odour binding and ion conduction domains, and provide a template for rationale structure-activity dissection.
authors.affiliation: 1] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Informatics, Technische Universität München, 85748 Garching, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hopf
authors.affiliation: 1] Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan [2] ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morinaga
authors.affiliation: 1] Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan [2] ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Ihara
authors.affiliation: 1] Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan [2] ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Touhara
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Debora S
authors.initials: DS
authors.lastname: Marks
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Benton
mesh_terms: D000596:Amino Acids / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D019143:Evolution, Molecular; D007313:Insecta / Q000378:metabolism*; D018035:Receptors, Odorant / Q000737:chemistry* / Q000235:genetics; D014981:Xenopus
chemical_list: D000596:Amino Acids; D018035:Receptors, Odorant