Data from: Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors

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Mammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled receptors expressed in olfactory cilia membranes. Most odorant receptors show little to no cell surface expression in non-olfactory cells due to endoplasmic reticulum retention, which has slowed down biochemical studies. Here, we provide evidence that structural instability and divergence from conserved residues of individual odorant receptors underlie intracellular retention using a combination of large-scale screening of odorant receptors cell surface expression in heterologous cells, point mutations, structural modeling, and machine learning techniques. We demonstrate the importance of conserved residues by synthesizing "consensus" odorant receptors that show high levels of cell surface expression similar to conventional G protein-coupled receptors. Furthermore, we associate in silico structural instability with poor cell surface expression using molecular dynamics simulations. We propose an enhanced evolutionary capacitance of olfactory sensory neurons that enable the functional expression of odorant receptors with cryptic mutations. ... [Read More]

Data Citation

Ikegami, K., de March, C. A., Nagai, M. H., Ghosh, S., Do, M., Sharma, R., ... Matsunami, H. (2019). Data from: Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors. Duke Digital Repository. https://doi.org/10.7924/r40867k2k

Creator: Lu, Yueyang Eric
de March, Claire A.
Ghosh, Soumadwip
Ikegami, Kentaro
Vaidehi, Nagarajan
Yohda, Masafumi
Fukutani, Yosuke
Sharma, Ruchira
Matsunami, Hiroaki
Do, Matthew
Bruguera, Elise S.
Nagai, Maira H.
DOI: 10.7924/r40867k2k
Subject: Molecular modeling
Structural analysis
Publication Date: December 19, 2019
ARK: ark:/87924/r40867k2k
Publisher: Duke Digital Repository
Collection Dates: 12/9/2019
Type: Dataset
Format: PDB
XLSX
Related Materials: Ikegami, K., De March, C. A., Nagai, M. H., Ghosh, S., Do, M., Sharma, R., . . . Matsunami, H. (2020). Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors. National Academy of Sciences, 117(6), 2957-2967. doi:10.1073/pnas.1915520117. https://doi.org/10.1073/pnas.1915520117
Funding Agency: NIH
Grant Number: R01-GM097261
DC014423
DC016224
Contact: Claire A. de March: claire.de.march@duke.edu, ORCID: 0000-0001-6461-5547
License: Creative Commons CC0 1.0 Universal
Title: Data from: Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors
License: http://creativecommons.org/publicdomain/zero/1.0/
Repository: Duke Research Data Repository

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