Structural bioinformatic study of six human olfactory receptors and their AlphaFold3 predicted water-soluble QTY variants and OR1A2 with an odorant octanoate and TAAR9 with spermidine
Name
structural-bioinformatic-study-of-six-human-olfactory-receptors-and-their-alphafold3-predicted-water-soluble-qty-variants-and-or1a2-with-an-odorant-octanoate-and-taar9-with-spermidine.pdf
Description
Published version
Size
3.84 MB
Format
Adobe PDF
Checksum (MD5)
dac0bfaa42307217991aa1c0c4a2c607
Author(s)
Johnsson, Finn
Karagöl, Taner
Karagöl, Alper
Zhang, Shuguang
Date Issued
December 9, 2024
Journal
QRB Discovery
Publisher
Cambridge University Press
Citation
Johnsson F, Karagöl T, Karagöl A, Zhang S. Structural bioinformatic study of six human olfactory receptors and their AlphaFold3 predicted water-soluble QTY variants and OR1A2 with an odorant octanoate and TAAR9 with spermidine. QRB Discovery. 2025;6:e2.
Version
Final published version
Abstract
The molecular mechanism of olfaction, namely, how we smell with limited olfactory receptors to recognize exceedingly diverse and large numbers of scents remains unknown despite the recent advances in chemistry, chemical, structural, and molecular biology. Olfactory receptors are notoriously difficult to study because they are fully embedded in the cell membrane. After decades of efforts and significant funding, there are only three olfactory receptor structures known. To understand olfaction, we carried out the structural bioinformatic study of six human olfactory receptors including OR51E1, OR51E2, OR52cs, OR1A1, OR1A2, TAAR9, and their AlphaFold3 predicted water-soluble QTY variants with odorants. We applied the QTY code to replace leucine (L) with glutamine (Q), isoleucine (I) and valine (V) with threonine (T), and phenylalanine (F) with tyrosine (Y) only in the transmembrane helices. Therefore, these QTY variants become water-soluble. We also present the superimposed structures of native olfactory receptors and their water-soluble QTY variants. The superimposed structures show remarkable similarity with RMSDs between 0.441 and 1.275 Å despite significant changes to the protein sequence of the transmembrane domains (43.03%–50.31%). We also show the differences in hydrophobicity surfaces between the native olfactory receptors and their QTY variants. Furthermore, we also used AlphaFold3 and molecular dynamics to study the odorant octanoate with OR1A2 and spermidine with TAAR9. Our bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices, and will likely further stimulate designs of water-soluble integral transmembrane proteins and other aggregated proteins.
MIT Department
Massachusetts Institute of Technology. Media Laboratory
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1017/qrd.2024.18
