Residue conservation and dimer-interface analysis of olfactory receptor molecular models

Krishnan Harini, Sankar Kannan, Wataru Nemoto, Kazuhiko Fukui, Ramanathan Sowdhamini


Olfactory Receptors (ORs) are members of the Class A rhodopsin like G-protein coupled receptors (GPCRs) which are the initial players in the signal transduction cascade, leading to the generation of nerve impulses transmitted to the brain and resulting in the detection of odorant molecules. Despite the accumulation of thousands of olfactory receptor sequences, no crystal structures of ORs are known tο date. However, the recent availability of crystallographic models of a few GPCRs allows us to generate homology models of ORs and analyze their amino acid patterns, as there is a huge diversity in OR sequences. In this study, we have generated three-dimensional models of 100 representative ORs from Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans and Sacharomyces cerevisiae which were selected on the basis of a composite classification scheme and phylogenetic analysis. The crystal structure of bovine rhodopsin was used as a template and it was found that the full-length models have more than 90% of their residues in allowed regions of the Ramachandran plot. The structures were further used for analysis of conserved residues in the transmembrane and extracellular loop regions in order to identify functionally important residues. Several ORs are known to be functional as dimers and hence dimer interfaces were predicted for OR models to analyse their oligomeric functional state.


olfaction; genome-wide survey; three-dimensional modelling; membrane proteins


Bardwell L 2004 A walk-through of the yeast mating pheromone response pathway. Peptides 25 1465-1476.

Benton R, Sachse S, Michnick SW & Vosshall LB 2006 Atypical Membrane Topology and Heteromeric Function of Drosophila Odorant Receptors In Vivo. PLoS Biol 4 e20.

Breer H., Fleischer J & Strotmann J 2006 The sense of smell: multiple olfactory subsystems Cell Mol Life Sci 63 1465-1475.

Buck L & Axel R 1991 A novel multigene family may encode odorant receptors: a molecular basis for odor recognition Cell 65 175-87.

Fleischer J, Breer H & Strotmann J 2009 Mammalian olfactory receptors. Front Cell Neurosci 3 9.

Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A & Palczewski K 2003 Atomic-force microscopy: rhodopsin dimers in native disc membranes. Nature 421 127-128.

Freitag J, Ludwig G, Andreini I, Rossler P & Breer H 1998 Olfactory receptors in aquatic and terrestrial vertebrates. J Comp Physiol A 183 635-650.

Freitag J, Krieger J, Strotmann J & Breer H 1995 Two classes of olfactory receptors in Xenopus laevis Neuron 15 1383-1392.

Glaser F, Pupko T, Paz I, Bell RE, Bechor D, Martz E & Ben-Tal N 2003 ConSurf: Identification of Functional Regions in Proteins by Surface-Mapping of Phylogenetic Information. Bioinformatics 19 163-164. Gottlieb A, Olender T, Lancet D & Horn D 2009 Common peptides shed light on evolution of Olfactory Receptors. BMC Evolutionary Biology 9 91.

Gouldson PR, Higgs C, Smith RE, Dean MK, Gkoutos GV & Reynolds CA 2000 Dimerization and domain swapping in G-protein-coupled receptors: a computational study Neuropsychopharmacology 23 S60-S77.

Jacoby E, Bouhelal R, Gerspacher M & Seuwen K 2006 The 7 TM G- protein- coupled receptor target family. Chem Med Chem 1 761-782.

Jorgensen WL 2004 The many roles of computation in drug discovery Science 303 1813-1818.

Katada S, Hirokawa T, Oka Y, Suwa M & Touhara K 2005 Structural basis for a broad but selective ligand spectrum of a mouse olfactory receptor: mapping the odorant-binding site. J Neurosci 25 1806-1815.

Landau M, Mayrose I, Rosenberg Y, Glaser F, Martz E, Pupko T & Ben-Tal N 2005 ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucl Acids Res 33 W299-W302.

Laskowski RA, MacArthur MW, Moss DS & Thornton JM 1993 PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26 283-291.

Mombaerts P 1999 Seven-Transmembrane Proteins as Odorant and Chemosensory Receptors. Science 286 707.

Nagarathnam B, Sankar K, Dharnidharka V, Balakrishnan V, Archunan G & Sowdhamini R 2011 TM-MOTIF: an alignment viewer to annotate predicted transmembrane helices and conserved motifs in aligned set of sequences. Bioinformation 7 214-221.

Nemoto W & Toh H 2005 Prediction of interfaces for oligomerizations of G-protein coupled receptors. PROTEINS: Struct Fun Bioinf 58 644-660.

Nemoto W & Toh H 2006 Membrane interactive α-helices in GPCRs, The biological role of membrane interactive amphiphilic α-helices. Cur Prot Pep Sci 7 561-575.

Nemoto W & Toh H 2009 GRIP: A server for predicting interfaces for GPCR oligomerization. J Recept Signal Transduct Res 29 312-7.

Nichols AS, Chen S, Charles W & Luetje CW 2011 Subunit Contributions to Insect Olfactory Receptor Function: Channel Block and Odorant Recognition. Chem Senses 36 781-790.

Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M & Miyano M 2000 Crystal structure of rhodopsin: A G-protein-coupled receptor. Science 289 739-745.

Pilpel Y & Lancet D 1999 The variable and conserved interfaces of modeled olfactory receptor proteins. Protein Science 8 969-977.

Pirovano W, Feenstra KA & Heringa J 2008. PRALINETM: a strategy for improved multiple alignment of transmembrane proteins. Bioinformatics 24 492-497.

Richon AB 2008 Current status and future direction of the molecular modeling industry. Drug Discov Today 13 665-669.

Sali A & Blundell TL 1993 Comparative protein modelling by satisfaction of spatial restraints J Mol Biol 234 779-815.

Tusndy GE & Simon I 2001 The HMMTOP transmembrane topology prediction server. Bioinformatics 17 849-850.

Waterhouse AM, Procter JB, Martin DMA, Clamp M & Barton GJ 2009 Jalview version 2: A Multiple Sequence Alignment and Analysis Workbench. Bioinformatics 25 1189-1191.

Ye Y & Godzik A 2003 Flexible structure alignment by chaining aligned fragment pairs allowing twists. Bioinformatics 19 246-255.

Full Text: PDF


  • There are currently no refbacks.

Copyright © 2014 Lorem Ipsum Press