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PreprintCited by 14Neurobiology and Insect Physiology ResearchInsect Pheromone Research and ControlReceptor Mechanisms and Signaling

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Two mosquito odorant receptors with reciprocal specificity mediated by a single amino acid residue

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Franco, Flávia P., Xu, Pingxi, Harris, Brandon J., Yarov-Yarovoy, Vladimir, Leal, Walter S.·2022·eLife
DOI 10.1101/2022.03.22.485336PMC PMC9799979

Preprint — published as 10.7554/elife.82922 · Paper page

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Abstract

The southern house mosquito, Culex quinquefasciatus , utilizes two odorant receptors, CquiOR10 and CquiOR2, narrowly tuned to oviposition attractants and well conserved among mosquito species. They detect skatole and indole, respectively, with reciprocal specificity. We swapped the seven transmembrane (TM) domains of CquiOR10 and CquiOR2 and identified TM2 as a specificity determinant. With additional mutations, we showed that CquiOR10A73L behaved like CquiOR2. Conversely, CquiOR2L74A recapitulated CquiOR10 specificity. Next, we generated structural models of CquiOR10 and CquiOR10A73L using RoseTTAFold and AlphaFold and docked skatole and indole using RosettaLigand. These modeling studies suggested space-filling constraints around A73. Consistent with this hypothesis, CquiOR10 mutants with a bulkier residue (Ile, Val) were insensitive to skatole and indole, whereas CquiOR10A73G retained the specificity to skatole and showed a more robust response than the wildtype receptor CquiOR10. On the other hand, Leu to Gly mutation of the indole receptor CquiOR2 reverted the specificity to skatole. Lastly, CquiOR10A73L, CquiOR2, and CquiOR2L74I were insensitive to 3-ethylindole, whereas CquiOR2L74A and CquiOR2L74G gained activity. Additionally, CquiOR10A73G gave more robust responses to 3-ethylindole than CquiOR10. Thus, we suggest the specificity of these receptors is mediated by a single amino acid substitution, leading to finely tuned volumetric space to accommodate specific oviposition attractants.

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Metadata

Authors
Franco, F. P., Xu, P., Harris, B. J., Yarov-Yarovoy, V., & Leal, W. S.
Affiliations
University of California, Davis (US)
Corresponding author
Leal, Walter S.
ORCID
Venue
eLife
Publisher
openRxiv
Published
2022-03-25
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.1101/2022.03.22.485336
PMC
PMC9799979
OpenAlex
W4311282532
Cited by
14
References
1
Citations by year
2026: 5 · 2025: 5 · 2024: 3 · 2023: 1
FWCI
0.99
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Vanderbilt University
  • National Institutes of Health
  • University of California, Davis
  • National Institute of General Medical Sciences (T32GM007377)
  • National Institute of Allergy and Infectious Diseases (R01AI095514)
  • Vanderbilt Institute of Chemical Biology, School of Medicine, Vanderbilt University
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Agricultural and Biological Sciences › Insect Science › Insect Pheromone Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
skatole, indole, oviposition attractants, transmembrane domain, single amino acid substitution, receptor structure modeling, protein-ligand docking
MeSH terms
Amino Acids, Animals, Female, Indoles, Culicidae, Oviposition, Skatole, Receptors, Odorant

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