TY - JOUR
T1 - An olfactory receptor pseudogene whose function emerged in humans
T2 - A case study in the evolution of structure-function in GPCRs
AU - Lai, Peter C.
AU - Bahl, Gautam
AU - Gremigni, Maryse
AU - Matarazzo, Valery
AU - Clot-Faybesse, Olivier
AU - Ronin, Catherine
AU - Crasto, Chiquito J.
N1 - Funding Information:
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.
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
KW - Computational modeling
KW - Docking
KW - Functional pseudogene
KW - Olfactory receptors
UR - http://www.scopus.com/inward/record.url?scp=57249095884&partnerID=8YFLogxK
U2 - 10.1007/s10969-008-9043-x
DO - 10.1007/s10969-008-9043-x
M3 - Article
C2 - 18802787
AN - SCOPUS:57249095884
SN - 1345-711X
VL - 9
SP - 29
EP - 40
JO - Journal of Structural and Functional Genomics
JF - Journal of Structural and Functional Genomics
IS - 1-4
ER -