Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3

Abstract Amino acid substitutions within the conserved polypeptide sequence of the insect olfactory receptor co-receptor (Orco) have been demonstrated to influence its pharmacological properties. By sequence analysis and phylogenetic investigation, in the Lepidopteran subgroup Ditrysia we identified...

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Autores principales:	Yuriy V. Bobkov, William B. Walker III, Alberto Maria Cattaneo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77dda03aad4c41d1b8660f9b6e62f5a0
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spelling	oai:doaj.org-article:77dda03aad4c41d1b8660f9b6e62f5a02021-12-02T14:03:56ZAltered functional properties of the codling moth Orco mutagenized in the intracellular loop-310.1038/s41598-021-83024-32045-2322https://doaj.org/article/77dda03aad4c41d1b8660f9b6e62f5a02021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83024-3https://doaj.org/toc/2045-2322Abstract Amino acid substitutions within the conserved polypeptide sequence of the insect olfactory receptor co-receptor (Orco) have been demonstrated to influence its pharmacological properties. By sequence analysis and phylogenetic investigation, in the Lepidopteran subgroup Ditrysia we identified a fixed substitution in the intracellular loop-3 (ICL-3) of a conserved histidine to glutamine. By means of HEK293 cells as a heterologous system, we functionally expressed Orco from the Ditrysian model Cydia pomonella (CpomOrco) and compared its functional properties with a site-directed mutagenized version where this ICL-3-glutamine was reverted to histidine (CpomOrcoQ417H). The mutagenized CpomOrcoQ417H displayed decreased responsiveness to VUAA1 and reduced response efficacy to an odorant agonist was observed, when co-transfected with the respective OR subunit. Evidence of reduced responsiveness and sensitivity to ligands for the mutagenized Orco suggest the fixed glutamine substitution to be optimized for functionality of the cation channel within Ditrysia. In addition, contrary to the wild type, the mutagenized CpomOrcoQ417H preserved characteristics of VUAA-binding when physiologic conditions turned to acidic. Taken together, our findings provide further evidence of the importance of ICL-3 in forming basic functional properties of insect Orco- and Orco/OR-channels, and suggest involvement of ICL-3 in the potential functional adaptation of Ditrysian Orcos to acidified extra-/intracellular environment.Yuriy V. BobkovWilliam B. Walker IIIAlberto Maria CattaneoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuriy V. Bobkov William B. Walker III Alberto Maria Cattaneo Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3
description	Abstract Amino acid substitutions within the conserved polypeptide sequence of the insect olfactory receptor co-receptor (Orco) have been demonstrated to influence its pharmacological properties. By sequence analysis and phylogenetic investigation, in the Lepidopteran subgroup Ditrysia we identified a fixed substitution in the intracellular loop-3 (ICL-3) of a conserved histidine to glutamine. By means of HEK293 cells as a heterologous system, we functionally expressed Orco from the Ditrysian model Cydia pomonella (CpomOrco) and compared its functional properties with a site-directed mutagenized version where this ICL-3-glutamine was reverted to histidine (CpomOrcoQ417H). The mutagenized CpomOrcoQ417H displayed decreased responsiveness to VUAA1 and reduced response efficacy to an odorant agonist was observed, when co-transfected with the respective OR subunit. Evidence of reduced responsiveness and sensitivity to ligands for the mutagenized Orco suggest the fixed glutamine substitution to be optimized for functionality of the cation channel within Ditrysia. In addition, contrary to the wild type, the mutagenized CpomOrcoQ417H preserved characteristics of VUAA-binding when physiologic conditions turned to acidic. Taken together, our findings provide further evidence of the importance of ICL-3 in forming basic functional properties of insect Orco- and Orco/OR-channels, and suggest involvement of ICL-3 in the potential functional adaptation of Ditrysian Orcos to acidified extra-/intracellular environment.
format	article
author	Yuriy V. Bobkov William B. Walker III Alberto Maria Cattaneo
author_facet	Yuriy V. Bobkov William B. Walker III Alberto Maria Cattaneo
author_sort	Yuriy V. Bobkov
title	Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3
title_short	Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3
title_full	Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3
title_fullStr	Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3
title_full_unstemmed	Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3
title_sort	altered functional properties of the codling moth orco mutagenized in the intracellular loop-3
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/77dda03aad4c41d1b8660f9b6e62f5a0
work_keys_str_mv	AT yuriyvbobkov alteredfunctionalpropertiesofthecodlingmothorcomutagenizedintheintracellularloop3 AT williambwalkeriii alteredfunctionalpropertiesofthecodlingmothorcomutagenizedintheintracellularloop3 AT albertomariacattaneo alteredfunctionalpropertiesofthecodlingmothorcomutagenizedintheintracellularloop3
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Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3

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