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
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 difficul...
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Cambridge University Press
2025-01-01
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| Series: | QRB Discovery |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S2633289224000188/type/journal_article |
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| author | Finn Johnsson Taner Karagöl Alper Karagöl Shuguang Zhang |
| author_facet | Finn Johnsson Taner Karagöl Alper Karagöl Shuguang Zhang |
| author_sort | Finn Johnsson |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b87b60dea250491daa28f16052c3af55 |
| institution | Kabale University |
| issn | 2633-2892 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | QRB Discovery |
| spelling | doaj-art-b87b60dea250491daa28f16052c3af552025-01-16T21:50:22ZengCambridge University PressQRB Discovery2633-28922025-01-01610.1017/qrd.2024.18Structural bioinformatic study of six human olfactory receptors and their AlphaFold3 predicted water-soluble QTY variants and OR1A2 with an odorant octanoate and TAAR9 with spermidineFinn Johnsson0https://orcid.org/0009-0009-9132-9488Taner Karagöl1https://orcid.org/0009-0005-1011-7661Alper Karagöl2https://orcid.org/0009-0001-7864-0732Shuguang Zhang3https://orcid.org/0000-0002-3856-3752St Paul’s School, Lonsdale Road, London SW13 9JT, UKIstanbul Medical Faculty, Istanbul University, Istanbul, TurkeyIstanbul Medical Faculty, Istanbul University, Istanbul, TurkeyLaboratory of Molecular Architecture, Media Lab, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USAThe 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.https://www.cambridge.org/core/product/identifier/S2633289224000188/type/journal_articlehydrophobic to hydrophilic conversionmembrane proteinsprotein designQTY codewater-soluble olfactory receptors |
| spellingShingle | Finn Johnsson Taner Karagöl Alper Karagöl Shuguang Zhang 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 hydrophobic to hydrophilic conversion membrane proteins protein design QTY code water-soluble olfactory receptors |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | hydrophobic to hydrophilic conversion membrane proteins protein design QTY code water-soluble olfactory receptors |
| url | https://www.cambridge.org/core/product/identifier/S2633289224000188/type/journal_article |
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