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Molecular reconstruction of recurrent evolutionary switching in olfactory receptor specificity
Open accessPublished version of a preprint
Abstract
Olfactory receptor repertoires exhibit remarkable functional diversity, but how these proteins have evolved is poorly understood. Through analysis of extant and ancestrally reconstructed drosophilid olfactory receptors from the Ionotropic receptor (Ir) family, we investigated evolution of two organic acid-sensing receptors, Ir75a and Ir75b. Despite their low amino acid identity, we identify a common ‘hotspot’ in their ligand-binding pocket that has a major effect on changing the specificity of both Irs, as well as at least two distinct functional transitions in Ir75a during evolution. Moreover, we show that odor specificity is refined by changes in additional, receptor-specific sites, including those outside the ligand-binding pocket. Our work reveals how a core, common determinant of ligand-tuning acts within epistatic and allosteric networks of substitutions to lead to functional evolution of olfactory receptors.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Metadata
- Authors
- Prieto-Godino, L. L., Schmidt, H. R., & Benton, R.
- Affiliations
- The Francis Crick Institute (GB)
- University of Lausanne (CH)
- Corresponding author
- Prieto-Godino, Lucia L
- Benton, Richard
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2021-10-22
- Volume
- 10
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC8575457
- OpenAlex
- W3206610810
- Cited by
- 31
- References
- 1
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 1
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by)
- IRIS (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- The Francis Crick Institute (cc-by)
- Funders
- EMBO (ALTF 940-2019)
- Helen Hay Whitney Foundation
- European Research Council (802531, 615094, 833548)
- Cancer Research UK (FC001594)
- Medical Research Council (FC001594)
- Wellcome Trust (FC001594)
- Swiss National Science Foundation (20NA21_143082)
- Human Frontier Science Program (RGY0073/2011)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- olfactory receptor evolution, ligand-gated ion channels, binding pocket, ancestral sequence reconstruction, epistasis, allosteric networks, Drosophila, functional transitions
- MeSH terms
- Animals, Drosophila melanogaster, Odorants, Olfactory Receptor Neurons, Receptors, Odorant, Evolution, Molecular
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