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  4. Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4
 
research article

Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4

Cook, B. L.
•
Steuerwald, D.
•
Kaiser, L.
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2009
Proceedings Of The National Academy Of Sciences Of The United States Of America (PNAS)

Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of > 10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be approximate to 50% alpha-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices.

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Type
research article
DOI
10.1073/pnas.0811089106
Web of Science ID

WOS:000268178400022

Author(s)
Cook, B. L.
Steuerwald, D.
Kaiser, L.
Graveland-Bikker, J.
Vanberghem, M.
Berke, A. P.
Herlihy, K.
Pick, H.  
Vogel, H.  
Zhang, S.
Date Issued

2009

Publisher

National Academy of Sciences

Published in
Proceedings Of The National Academy Of Sciences Of The United States Of America (PNAS)
Volume

106

Issue

29

Start page

11925

End page

11930

Subjects

BiacoreA100

•

detergent screen

•

fos-choline 14

•

G protein-coupled receptor purification

•

membrane protein

•

High-Level Expression

•

Circular-Dichroism Spectra

•

Mammalian-Cell Lines

•

Secondary Structure

•

Ligand-Binding

•

Opsin Gene

•

Rhodopsin

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Glycosylation

•

Purification

•

Mutants

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
LCPPM  
Available on Infoscience
April 30, 2010
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/49871
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