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An olfactory receptor pseudogene whose function emerged in humans: a case study in the evolution of structure–function in GPCRs

  • Published:
Journal of Structural and Functional Genomics

Abstract

Human olfactory receptor, hOR17-210, is identified as a pseudogene in the human genome. Experimental data has shown however, that the gene product of frame-shifted, cloned hOR17-210 cDNA was able to bind an odorant-binding protein and is narrowly tuned for excitation by cyclic ketones. Supported by experimental results, we used the bioinformatics methods of sequence analysis (genome-wide and pair-wise), computational protein modeling and docking, to show that functionality in this receptor is retained due to sequence-structure features not previously observed in mammalian ORs. This receptor does not possess the first two transmembrane helical domains (of seven typically seen in GPCRs). It however, possesses an additional TM that has not been observed in other human olfactory receptors. By incorporating these novel structural features, we created two putative models for this receptor. We also docked odor ligands that were experimentally shown to bind hOR17-210. We show how and why structural modifications of OR17-210 do not hinder this receptor’s functionality. Our studies reveal that novel gene rearrangements that result in sequence and structural diversity may have a bearing on OR and GPCR function and evolution.

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Abbreviations

OR:

Olfactory Receptors

GPCR:

GTP-binding Protein Coupled Receptors

HUGO:

Human Genome Organization

HORDE:

Human Olfactory Receptor Database Exploratorium

SPHGEN:

Sphere Generator

CVFF:

Consistent Valence Force Field

DMS:

Dot Molecular Surface

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Acknowledgements

This work was generously supported by Grant 2 P01 DC 004732-05 from the National Institute for Deafness and Communicative Disorders, National Institutes of Health. P. L. was supported as a part-time undergraduate researcher at the Department of Neurobiology, Yale University School of Medicine. This work is also supported by a Faculty Development Grant (CC) at the University of Alabama at Birmingham.

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Author notes

  1. Chiquito J. Crasto

    Present address: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

Authors and Affiliations

  1. Division of Natural Science, Mathematics, and Computing, Bard College at Simon’s Rock, Great Barrington, MA, USA

    Peter C. Lai

  2. Department of Radiology, Wayne State University/Detroit Medical Center, Detroit, MI, USA

    Gautam Bahl

  3. Laboratoire de Neuroglycobiologie, UMR 6149 CNRS, Université de Provence, Pole 3C, 3 Pl. V.Hugo, 13331, Marseille Cedex 3, France

    Maryse Gremigni, Valery Matarazzo, Olivier Clot-Faybesse & Catherine Ronin

  4. Department of Neurobiology, Yale University School of Medicine, New Haven, CT, 06516, USA

    Chiquito J. Crasto

  5. Yale Center for Medical Informatics, Yale University School of Medicine, New Haven, CT, 06516, USA

    Chiquito J. Crasto

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  1. Peter C. Lai
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Correspondence to Chiquito J. Crasto.

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Lai, P.C., Bahl, G., Gremigni, M. et al. An olfactory receptor pseudogene whose function emerged in humans: a case study in the evolution of structure–function in GPCRs. J Struct Funct Genomics 9, 29–40 (2008). https://doi.org/10.1007/s10969-008-9043-x

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  • DOI: https://doi.org/10.1007/s10969-008-9043-x

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