Skip to main content
SpringerLink
Log in
Book cover

Chemical Signals in Vertebrates 14 pp 221–237Cite as

Comparative Structural Modeling of Bovine Vomeronasal Type-1 Receptor 1 (VN1R1) and Elucidation of Molecular Interactions with Pheromones Using in silico Approaches

  • Conference paper
  • First Online:

  • 484 Accesses

Abstract

The perception of pheromone signals is mediated by the axon of chemosensory neurons in the vomeronasal organ (VNO ) that project into the accessory olfactory bulb (AOB ) in the nasal cavity. Specifically, the vomeronasal type-1 receptor 1 (VN1R1 ) is a member of the G protein-coupled receptor (GPCR) superfamily of proteins and interconnecting large olfactory sensory neurons that is directed by a multigene superfamily in most species. In bovines, the VN1R1 is crucially involved in mate choice , reproduction and pheromone transport activity during chemical communication . The VNO morphology , genome assembly, sequence alignment and evolutionary divergence of VN1R were described previously. However, the structural modeling and elucidation of bovine VN1R1 protein have not yet been reported. In this study, we aimed to perform sequence analysis , structure prediction and function elucidation using computational methods. The results revealed that (i) the highest proportions of α-helix and random coils were observed in several structural and functionally conserved sites of VN1R1 ; (ii) the comparative template-based VN1R1 model was predicted with >93% of the most favoured region in the Ramachandran Plot validation; (iii) with regard to the transmembrane topology , structural superimposition was additionally supported by the bovine VN1R1 computational model; and (iv) the molecular interactions of pheromones and VN1R1 output suggested the best-fit endogenous ligand ‘p-Cresol ’, which is suitable for the binding of a VN1R1 model. For the first time, we performed comparative structure prediction of the bovine VN1R1 model to identify the putative isoforms of pheromones involved in signal transduction in animal reproduction and management.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Albone ES (1984) Mammalian semiochemistry: the investigation of chemical signals between mammals. Wiley, New York

    Google Scholar 

  • Albone ES, Blazquez NB, French J, Long SE, Perry GC (1986) Mammalian semiochemistry: issues and futures, with some examples from a study of chemical signalling in cattle. In: Duvall D, Müller-Schwarze D, Silverstein RM (eds) Chemical signals in vertebrates 4. Springer, Boston, MA, pp 27–36

    Chapter  Google Scholar 

  • Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  CAS  Google Scholar 

  • Archunan G (2009) Vertebrate pheromones and their biological importance. J Exp Zool India 12:227–239

    Google Scholar 

  • Archunan G, Rajanarayanan S (2010) Composition for enhancing bull sex libido. Indian Patent No. 244991, 28 Dec 2010

    Google Scholar 

  • Archunan G, Rameshkumar K (2012) 1-Iodoundecae an estrus indicating urinary chemosignal in bovine (Bos taurus). J Vet Sci Tech 3:121–123

    Article  Google Scholar 

  • Berezin C, Glaser F, Rosenberg J, Paz I, Pupko T, Fariselli P, Casadio R, Ben-Tal N (2004) ConSeq: the identification of functionally and structurally important residues in protein sequences. Bioinformatics 20:1322–1324

    Article  CAS  Google Scholar 

  • Bikadi Z, Hazai E (2009) Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock. J Cheminform 1:1–16

    Article  Google Scholar 

  • Buck L, Axel R (1991) A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65:175–187

    Article  CAS  Google Scholar 

  • Buck LB (2000) The molecular architecture of review odor and pheromone sensing in mammals. Cell 100:611–618

    Article  CAS  Google Scholar 

  • BūdaV Mozūraitis R, Kutra J, Borg-Karlson AK (2012) p-Cresol: a sex pheromone component identified from the estrous urine of mares. J Chem Ecol 38:811–813

    Article  Google Scholar 

  • Dulac C, Axel R (1995) A novel family of genes encoding putative pheromone receptors in mammals. Cell 83:195–206

    Article  CAS  Google Scholar 

  • Dulac C, Axel R (1998) Expression of Candidate pheromone receptor genes in vomeronasal Neurons. Chem Senses 23:467–475

    Article  CAS  Google Scholar 

  • Dulac C, Torello AT (2003) Molecular detection of pheromone signals in mammals: from genes to behaviour. Nat Rev Neurosci 4:551–562

    Article  CAS  Google Scholar 

  • Geourjon C, Deléage G (1995) SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Bioinformatics 11:681–684

    Article  CAS  Google Scholar 

  • Glaser F, Pupko T, Paz I, Bell RE, Bechor-Schental D, Martz E, Ben-Tal N (2003) ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics 19:163–164

    Article  CAS  Google Scholar 

  • Godzik A (2003) Fold recognition methods. Methods Biochem Anal 44:525–546

    CAS  PubMed  Google Scholar 

  • Golebiowski J, Topin J, Charlier L (2012) Interaction between odorants and proteins involved in the perception of smell: the case of odorant-binding proteins probed by molecular modelling and biophysical data. Flavour Fragr J 27:445–453

    Article  CAS  Google Scholar 

  • Harini K, Sowdhamini R (2015) Computational approaches for decoding select odorant-olfactory receptor interactions using mini-virtual screening. PLoS ONE 10:1–30

    Article  Google Scholar 

  • Herrada G, Dulac C (1997) A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 90:763–773

    Article  CAS  Google Scholar 

  • Jones DT, Taylor WR, Thornton JM (1992) The rapid generation of mutation data matricies from protein sequences. Comput Appl Biosci 8:275–282

    CAS  PubMed  Google Scholar 

  • Källberg M, Wang H, Wang S (2012) Template-based protein structure modeling using the RaptorX web server. Nat Protoc 7:1511–1522

    Article  Google Scholar 

  • Karlson P, Lüscher M (1959) “Pheromones”: a new term for a class of biologically active substances. Nature 183:55–56

    Article  CAS  Google Scholar 

  • Karthikeyan K, Archunan G (2013) Gas chromatographic mass spectrometric analysis of estrus-specific volatile compounds in buffalo vaginal mucus after initial sexual foreplay. J Buffalo Sci 2:1–7

    CAS  Google Scholar 

  • Karthikeyan K, Manivannan P, Rajesh D, Muthukumar S, Muralidharan G, Akbarsha MA, Archunan G (2014) Identification of p-cresol as an estrus-specific volatile in buffalo saliva: comparative docking analysis of buffalo OBP and β-lactoglobulin with p-cresol. Zoolog Sci 31:31–36

    Article  CAS  Google Scholar 

  • Kekan PM, Ingole SD, Sirsat SD, Bharucha SV, Kharde SD, Nagvekar AS (2017) The role of pheromones in farm animals-a review. Agri Rev 38:83–93

    Article  Google Scholar 

  • Keverne EB (1999) The vomeronasal organ. Handbook of olfaction gustation, vol 286, pp 967–980

    Google Scholar 

  • Kubo H, Otsuka M, Kadokawa H (2016) Sexual polymorphisms of vomeronasal 1 receptor family gene expression in bulls, steers, and estrous and early luteal-phase heifers. J Vet Med Sci 78:271–279

    Article  CAS  Google Scholar 

  • Kumar KR, Archunan G, Jeyaraman R, Narasimhan S (2000) Chemical characterization of bovine urine with special reference to oestrus. Vet Res Commun 24:445–454

    Article  CAS  Google Scholar 

  • Kuriata A, Gierut AM, Oleniecki T, Ciemny MP, Kolinski A, Kurcinski M, Kmiecik S (2018) CABS-flex 2.0: a web server for fast simulations of flexibility of protein structures. Nucleic Acids Res 46:338–343

    Article  Google Scholar 

  • 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. Nucleic Acids Res 33:299–302

    Article  Google Scholar 

  • Laskowski RA, MacArthur MW, Moss DS (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291

    Article  CAS  Google Scholar 

  • Laskowski RA, Watson JD, Thornton JM (2005) ProFunc: a server for predicting protein function from 3D structure. Nucleic Acids Res 33:89–93

    Article  Google Scholar 

  • Le Danvic C, Gérard O, Sellem E, Ponsart C, Chemineau P, Humblot P, Nagnan-Le Meillour P (2015) Enhancing bull sexual behavior using estrus-specific molecules identified in cow urine. Theriogenology 83:1381–1388

    Article  Google Scholar 

  • Ma J, Wang S, Zhao F, Xu J (2013) Protein threading using context-specific alignment potential. Bioinformatics 29:257–265

    Article  Google Scholar 

  • Matsunami H, Buck LB (1997) A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90:775–784

    Article  CAS  Google Scholar 

  • Mirkovic N, Li Z, Parnassa A, Murray D (2007) Strategies for high-throughput comparative modeling: applications to leverage analysis in structural genomics and protein family organization. Proteins 66:766–777

    Article  CAS  Google Scholar 

  • Mombaerts P (2004) Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 5:263–278

    Article  CAS  Google Scholar 

  • Mombearts P (1999) Seven-transmembrane proteins as odorants and chemosensory receptors. Science 286:707–711

    Article  Google Scholar 

  • Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639–1662

    Article  CAS  Google Scholar 

  • Morris GM, Goodsell DS, Pique ME, Lindstrom W, Huey R, Forli S, Hart WE, Halliday S Belew R, Olson AJ (2009) AutoDock version 4.2. User guide 1–49. http://autodock.scripps.edu/faqs-help/manual/autodock-4-2-user-guide. Accessed 18 Dec 2018

  • Mozūraitis R, Kutra J, Borg-Karlson AK, Būda V (2017) Dynamics of putative sex pheromone components during heat periods in estrus-induced cows. J Dairy Sci 100:7686–7695

    Article  Google Scholar 

  • Murakami M, Kouyama T (2008) Crystal structure of squid rhodopsin. Nature 453:363–367

    Article  CAS  Google Scholar 

  • Muthukumar S, Rajesh D, Selvam RM, Saibaba G, Suvaithenamudhan S, Akbarsha MA, Padmanabhan P, Gulyas B, Archunan G (2018) Buffalo nasal odorant-binding protein (bunOBP) and its structural evaluation with putative pheromones. Sci Rep 8:9323

    Article  Google Scholar 

  • Ohara H, Nikaido M, Date-Ito A, Mogi K, Okamura H, Okada N, Takeuchi Y, Mori Y, Hagino-Yamagishi K (2009) Conserved repertoire of orthologous vomeronasal type 1 receptor genes in ruminant species. BMC Evol Biol 9:233

    Article  Google Scholar 

  • Omasits U, Ahrens CH, Müller S, Wollscheid B (2014) Protter: interactive protein feature visualization and integration with experimental proteomic data. Bioinformatics 30:884–886

    Article  CAS  Google Scholar 

  • Osella MC, Cozzi A, Spegis C, Turille G, Barmaz A, Lecuelle CL, Teruel E, Bienboire-Frosini C, Chabaud C, Bougrat L, Pageat P (2018) The effects of a synthetic analogue of the Bovine Appeasing Pheromone on milk yield and composition in Valdostana dairy cows during the move from winter housing to confined lowland pastures. J Dairy Res 85:174–177

    Article  CAS  Google Scholar 

  • Pageat P (1998) Appeasing pheromones to decrease stress, anxiety and aggressiveness. European patent EP 0 948 963 A1; US Patent 6,054,481; US Patent 6,077,867; US Patent US 6,169,113 B1; Japan Patent 2000-528279; Japan Patent 980298

    Google Scholar 

  • Papes F, Logan DW, Stowers L (2010) The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141:692–703

    Article  CAS  Google Scholar 

  • Patra MK, Barman P, Kumar H (2012) Potential application of pheromones in reproduction of farm animals–a review. Agri Rev 33:82–86

    Google Scholar 

  • Peng J, Xu J (2011) A multiple-template approach to protein threading. Proteins 79:1930–1939

    Article  CAS  Google Scholar 

  • Rajanarayanan S, Archunan G (2011) Identification of urinary sex pheromones in female buffaloes and their influence on bull reproductive behaviour. Res Vet Sci 91:301–305

    Article  CAS  Google Scholar 

  • Rajesh D, Muthukumar S, Saibaba G, Siva D, Akbarsha MA, Gulyas B, Padmanabhan P, Archunan G (2016) Structural elucidation of estrus urinary lipocalin protein (EULP) and evaluating binding affinity with pheromones using molecular docking and fluorescence study. Sci Rep 6:35900

    Article  CAS  Google Scholar 

  • Robert X, Gouet P (2014) Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res 42:320–324

    Article  Google Scholar 

  • Rodriguez I, Greer CA, Mok MY, Mombaerts P (2000) A putative pheromone receptor gene expressed in human olfactory mucosa. Nat Genet 26:18–19

    Article  CAS  Google Scholar 

  • Rodriguez I, Mombaerts P (2002) Novel human vomeronasal receptor-like genes reveal species-specific families. Curr Biol 12:409–411

    Article  Google Scholar 

  • Rodriguez I (2003) Nosing into pheromone detectors. Nat Neurosci 6:438–440

    Article  CAS  Google Scholar 

  • Rost B (1999) Twilight zone of protein sequence alignments. Protein Eng 12:85–94

    Article  CAS  Google Scholar 

  • Ryba NJP, Tirindelli R (1997) A new multigene family of putative pheromone receptors. Neuron 19:371–379

    Article  CAS  Google Scholar 

  • Shimamura T, Hiraki K, Takahashi N, Hori T, Ago H, Masuda K, Takio K, Ishiguro M, Miyano M (2008) Crystal structure of squid rhodopsin with intracellularly extended cytoplasmic region. J Biol Chem 283:17753–17756

    Article  CAS  Google Scholar 

  • Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729

    Article  CAS  Google Scholar 

  • Tian W, Chen C, Lei X, Zhao J, Liang J (2018) CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res 1–5

    Google Scholar 

  • Tirindelli R, Dibattista M, Pifferi S, Menini A (2009) From pheromones to behavior. Physiol Rev 89:921–956

    Article  CAS  Google Scholar 

  • Vyas S, Briant C, Chemineau P, Danvic Le, Nagnan-Le Meillour P (2012) Oestrus pheromones in farm mammals, with special reference to cow. Indian J Anim Sci 82:256–267

    CAS  Google Scholar 

  • Wakabayashi Y, Mori Y, Ichikawa M, Yazaki K, Hagino-Yamagishi K (2002) A putative pheromone receptor gene is expressed in two distinct olfactory organs in goats. Chem Senses 27:207–213

    Article  CAS  Google Scholar 

  • Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127–134

    Article  CAS  Google Scholar 

  • Wyatt TD (2010) Pheromones and signature mixtures: defining species-wide signals and variable cues for identity in both invertebrates and vertebrates. J Comp Physiol A 196:685–700

    Article  CAS  Google Scholar 

  • Wyatt TD (2014) Proteins and peptides as pheromone signals and chemical signatures. Anim Behav 97:273–280

    Article  Google Scholar 

  • Wyatt TD (2017) Pheromones. Curr Biol 27:739–743

    Article  Google Scholar 

  • Yoder AD, Larsen PA (2014) The molecular evolutionary dynamics of the vomeronasal receptor (class 1) genes in primates: a gene family on the verge of a functional breakdown. Front Neuroanat 8:1–9

    Article  Google Scholar 

  • Young JM, Massa HF, Hsu L, Trask BJ (2010) Extreme variability among mammalian V1R gene families. Genome Res 20:10–18

    Article  CAS  Google Scholar 

  • Zufall F, Munger SD (2001) From odor and pheromone transduction to the organization of the sense of smell. Trends Neurosci 24:191–193

    Article  CAS  Google Scholar 

Download references

Acknowledgements

DR gratefully thanks the Research Institute in Semiochemistry and Applied Ethology (IRSEA), APT, France, for infrastructural facilities and support. We thank Dr. Christina D. Buesching and Dr. Carsten T. Mueller for providing valuable suggestions to improve the manuscript. We thank the Council of Research Education Board Members, IRSEA for valuable discussion and critical reading of this manuscript.

Author information

Authors and Affiliations

  1. Department of Behavioural and Physiological Mechanisms of Adaptation (D-MPCA), Research Institute in Semiochemistry and Applied Ethology (IRSEA), Quartier Salignan, 84400, Apt, France

    Rajesh Durairaj & Cécile Bienboire-Frosini

  2. Department of Chemicals Identification and Development of Analogues, Research Institute in Semiochemistry and Applied Ethology (IRSEA), Quartier Salignan, Apt, France

    Patrick Pageat

Authors
  1. Rajesh Durairaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cécile Bienboire-Frosini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick Pageat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajesh Durairaj .

Editor information

Editors and Affiliations

  1. Wildlife Conservation Research Unit, Department of Zoology, University of Oxford, Abingdon, Oxfordshire, UK

    Christina D. Buesching

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Durairaj, R., Bienboire-Frosini, C., Pageat, P. (2019). Comparative Structural Modeling of Bovine Vomeronasal Type-1 Receptor 1 (VN1R1) and Elucidation of Molecular Interactions with Pheromones Using in silico Approaches. In: Buesching, C. (eds) Chemical Signals in Vertebrates 14. Springer, Cham. https://doi.org/10.1007/978-3-030-17616-7_16

Download citation

Publish with us

Policies and ethics

Search

Navigation