An olfactory receptor pseudogene whose function emerged in humans: a case study in the evolution of structure-function in GPCRs.
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.
Lai
Peter C
PC
Division of Natural Science, Mathematics, and Computing, Bard College at Simon's Rock, Great Barrington, MA, USA.
Bahl
Gautam
G
Gremigni
Maryse
M
Matarazzo
Valery
V
Clot-Faybesse
Olivier
O
Ronin
Catherine
C
Crasto
Chiquito J
CJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D019992:Databases as Topic; D019143:Evolution, Molecular; D006801:Humans; D008390:Markov Chains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011544:Pseudogenes; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics*
D018076:DNA, Complementary; D043562:Receptors, G-Protein-Coupled; D018035:Receptors, Odorant