Home Engineered odorant receptors illuminate the basis of odour discrimination

Engineered odorant receptors illuminate the basis of odour discrimination

  1. Buck, L. & Axel, R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65, 175–187 (1991).
  2. CAS PubMed MATH  Google Scholar 
  3. Glusman, G., Yanai, I., Rubin, I. & Lancet, D. The complete human olfactory subgenome. Genome Res. 11, 685–702 (2001).
  4. CAS PubMed MATH  Google Scholar 
  5. Ikegami, K. et al. Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors. Proc. Natl Acad. Sci. USA 117, 2957–2967 (2020).
  6. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  7. Malnic, B., Godfrey, P. A. & Buck, L. B. The human olfactory receptor gene family. Proc. Natl Acad Sci. USA 101, 2584–2589 (2004).
  8. ADS CAS PubMed PubMed Central  Google Scholar 
  9. Bjarnadóttir, T. K. et al. Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Genomics 88, 263–273 (2006).
  10. PubMed MATH  Google Scholar 
  11. Liberles, S. D. & Buck, L. B. A second class of chemosensory receptors in the olfactory epithelium. Nature 442, 645–650 (2006).
  12. ADS CAS PubMed  Google Scholar 
  13. Olender, T., Jones, T. E. M., Bruford, E. & Lancet, D. A unified nomenclature for vertebrate olfactory receptors. BMC Evol. Biol. 20, 42 (2020).
  14. CAS PubMed PubMed Central  Google Scholar 
  15. Malnic, B., Hirono, J., Sato, T. & Buck, L. B. Combinatorial receptor codes for odors. Cell 96, 713–723 (1999).
  16. CAS PubMed  Google Scholar 
  17. Saito, H., Chi, Q., Zhuang, H., Matsunami, H. & Mainland, J. D. Odor coding by a mammalian receptor repertoire. Sci. Signal. 2, ra9 (2009).
  18. PubMed PubMed Central  Google Scholar 
  19. Cichy, A., Shah, A., Dewan, A., Kaye, S. & Bozza, T. Genetic depletion of class I odorant receptors impacts perception of carboxylic acids. Curr. Biol. 29, 2687–2697.e4 (2019).
  20. CAS PubMed PubMed Central  Google Scholar 
  21. Dewan, A., Pacifico, R., Zhan, R., Rinberg, D. & Bozza, T. Non-redundant coding of aversive odours in the main olfactory pathway. Nature 497, 486–489 (2013).
  22. ADS CAS PubMed PubMed Central  Google Scholar 
  23. Niimura, Y. On the origin and evolution of vertebrate olfactory receptor genes: comparative genome analysis among 23 chordate species. Genome Biol. Evol. 1, 34–44 (2009).
  24. PubMed PubMed Central MATH  Google Scholar 
  25. Bear, D. M., Lassance, J.-M., Hoekstra, H. E. & Datta, S. R. The evolving neural and genetic architecture of vertebrate olfaction. Curr. Biol. 26, R1039–R1049 (2016).
  26. CAS PubMed PubMed Central  Google Scholar 
  27. Freitag, J., Krieger, J., Strotmann, J. & Breer, H. Two classes of olfactory receptors in Xenopus laevis. Neuron 15, 1383–1392 (1995).
  28. CAS PubMed  Google Scholar 
  29. Billesbølle, C. B. et al. Structural basis of odorant recognition by a human odorant receptor. Nature 615, 742–749 (2023).
  30. ADS PubMed PubMed Central MATH  Google Scholar 
  31. Guo, L. et al. Structural basis of amine odorant perception by a mammal olfactory receptor. Nature 618, 193–200 (2023).
  32. ADS CAS PubMed MATH  Google Scholar 
  33. Shang, P. et al. Structural and signaling mechanisms of TAAR1 enabled preferential agonist design. Cell 186, 5347–5362.e24 (2023).
  34. CAS PubMed MATH  Google Scholar 
  35. Xu, Z. et al. Ligand recognition and G-protein coupling of trace amine receptor TAAR1. Nature 624, 672–681 (2023).
  36. ADS CAS PubMed MATH  Google Scholar 
  37. Liu, H. et al. Recognition of methamphetamine and other amines by trace amine receptor TAAR1. Nature 624, 663–671 (2023).
  38. ADS CAS PubMed MATH  Google Scholar 
  39. Gusach, A. et al. Molecular recognition of an odorant by the murine trace amine-associated receptor TAAR7f. Nat. Commun. 15, 7555 (2024).
  40. CAS PubMed PubMed Central MATH  Google Scholar 
  41. Lu, M., Echeverri, F. & Moyer, B. D. Endoplasmic reticulum retention, degradation, and aggregation of olfactory G-protein coupled receptors. Traffic 4, 416–433 (2003).
  42. CAS PubMed  Google Scholar 
  43. Saito, H., Kubota, M., Roberts, R. W., Chi, Q. & Matsunami, H. RTP family members induce functional expression of mammalian odorant receptors. Cell 119, 679–691 (2004).
  44. CAS PubMed  Google Scholar 
  45. Zhuang, H. & Matsunami, H. Evaluating cell-surface expression and measuring activation of mammalian odorant receptors in heterologous cells. Nat. Protoc. 3, 1402–1413 (2008).
  46. CAS PubMed PubMed Central MATH  Google Scholar 
  47. Noe, F. et al. IL-6-HaloTag® enables live-cell plasma membrane staining, flow cytometry, functional expression, and de-orphaning of recombinant odorant receptors. J. Biol. Methods 4, e81 (2017).
  48. PubMed PubMed Central MATH  Google Scholar 
  49. Sternke, M., Tripp, K. W. & Barrick, D. Consensus sequence design as a general strategy to create hyperstable, biologically active proteins. Proc. Natl Acad. Sci. USA 116, 11275–11284 (2019).
  50. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  51. Desjarlais, J. R. & Berg, J. M. Use of a zinc-finger consensus sequence framework and specificity rules to design specific DNA binding proteins. Proc. Natl Acad. Sci. USA 90, 2256–2260 (1993).
  52. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  53. Porebski, B. T. & Buckle, A. M. Consensus protein design. Protein Eng. Des. Sel. 29, 245–251 (2016).
  54. CAS PubMed PubMed Central MATH  Google Scholar 
  55. Steipe, B., Schiller, B., Plückthun, A. & Steinbacher, S. Sequence statistics reliably predict stabilizing mutations in a protein domain. J. Mol. Biol. 240, 188–192 (1994).
  56. CAS PubMed  Google Scholar 
  57. Lehmann, M. et al. From DNA sequence to improved functionality: using protein sequence comparisons to rapidly design a thermostable consensus phytase. Protein Eng. 13, 49–57 (2000).
  58. CAS PubMed MATH  Google Scholar 
  59. Choi, C. et al. Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family. Nat. Commun. 14, 8105 (2023).
  60. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  61. Nehmé, R. et al. Mini-G proteins: novel tools for studying GPCRs in their active conformation. PLoS ONE 12, e0175642 (2017).
  62. PubMed PubMed Central  Google Scholar 
  63. Ballesteros, J. A. & Weinstein, H. in Methods in Neurosciences Vol. 25 (ed. Sealfon, S. C.) 366–428 (Academic Press, 1995).
  64. de March, C. A., Kim, S.-K., Antonczak, S., Goddard, W. A. 3rd & Golebiowski, J. G protein-coupled odorant receptors: from sequence to structure. Protein Sci. 24, 1543–1548 (2015).
  65. PubMed PubMed Central  Google Scholar 
  66. Isberg, V. et al. Generic GPCR residue numbers—aligning topology maps while minding the gaps. Trends Pharmacol. Sci. 36, 22–31 (2015).
  67. CAS PubMed  Google Scholar 
  68. de March, C. A. et al. Conserved residues control activation of mammalian G protein-coupled odorant receptors. J. Am. Chem. Soc. 137, 8611–8616 (2015).
  69. PubMed PubMed Central MATH  Google Scholar 
  70. Pluznick, J. L. et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc. Natl Acad. Sci. USA 110, 4410–4415 (2013).
  71. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  72. Shayya, H. J. et al. ER stress transforms random olfactory receptor choice into axon targeting precision. Cell 185, 3896–3912.e22 (2022).
  73. CAS PubMed PubMed Central MATH  Google Scholar 
  74. Mainland, J. D., Li, Y. R., Zhou, T., Liu, W. L. L. & Matsunami, H. Human olfactory receptor responses to odorants. Sci. Data 2, 150002 (2015).
  75. CAS PubMed PubMed Central  Google Scholar 
  76. Kajiya, K. et al. Molecular bases of odor discrimination: reconstitution of olfactory receptors that recognize overlapping sets of odorants. J. Neurosci. 21, 6018–6025 (2001).
  77. CAS PubMed PubMed Central MATH  Google Scholar 
  78. Grosmaitre, X. et al. SR1, a mouse odorant receptor with an unusually broad response profile. J. Neurosci. 29, 14545–14552 (2009).
  79. CAS PubMed PubMed Central MATH  Google Scholar 
  80. Schmiedeberg, K. et al. Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2. J. Struct. Biol. 159, 400–412 (2007).
  81. CAS PubMed MATH  Google Scholar 
  82. Geithe, C., Noe, F., Kreissl, J. & Krautwurst, D. The broadly tuned odorant receptor OR1A1 is highly selective for 3-methyl-2,4-nonanedione, a key food odorant in aged wines, tea, and other foods. Chem. Senses 42, 181–193 (2017).
  83. CAS PubMed  Google Scholar 
  84. Ma, N., Lee, S. & Vaidehi, N. Activation microswitches in adenosine receptor A2A function as rheostats in the cell membrane. Biochemistry 59, 4059–4071 (2020).
  85. CAS PubMed MATH  Google Scholar 
  86. Dror, R. O. et al. Activation mechanism of the β2-adrenergic receptor. Proc. Natl Acad. Sci. USA 108, 18684–18689 (2011).
  87. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  88. Lee, S., Nivedha, A. K., Tate, C. G. & Vaidehi, N. Dynamic role of the G protein in stabilizing the active state of the adenosine A2A receptor. Structure 27, 703–712.e3 (2019).
  89. CAS PubMed PubMed Central  Google Scholar 
  90. Li, Q. et al. Non-classical amine recognition evolved in a large clade of olfactory receptors. eLife 4, e10441 (2015).
  91. PubMed PubMed Central  Google Scholar 
  92. Del Mármol, J., Yedlin, M. A. & Ruta, V. The structural basis of odorant recognition in insect olfactory receptors. Nature 597, 126–131 (2021).
  93. ADS PubMed PubMed Central  Google Scholar 
  94. Butterwick, J. A. et al. Cryo-EM structure of the insect olfactory receptor Orco. Nature 560, 447–452 (2018).
  95. ADS CAS PubMed PubMed Central  Google Scholar 
  96. Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
  97. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  98. Bender, B. J., Marlow, B. & Meiler, J. Improving homology modeling from low-sequence identity templates in Rosetta: a case study in GPCRs. PLoS Comput. Biol. 16, e1007597 (2020).
  99. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  100. Rutherford, S. L. & Lindquist, S. Hsp90 as a capacitor for morphological evolution. Nature 396, 336–342 (1998).
  101. ADS CAS PubMed MATH  Google Scholar 
  102. Wyganowski, K. T., Kaltenbach, M. & Tokuriki, N. GroEL/ES buffering and compensatory mutations promote protein evolution by stabilizing folding intermediates. J. Mol. Biol. 425, 3403–3414 (2013).
  103. CAS PubMed  Google Scholar 
  104. Agozzino, L. & Dill, K. A. Protein evolution speed depends on its stability and abundance and on chaperone concentrations. Proc. Natl Acad. Sci. USA 115, 9092–9097 (2018).
  105. ADS CAS PubMed PubMed Central MATH  Google Scholar 
  106. Faust, B. et al. Autoantibody mimicry of hormone action at the thyrotropin receptor. Nature 609, 846–853 (2022).
  107. Mastronarde, D. N. SerialEM: a program for automated tilt series acquisition on Tecnai microscopes using prediction of specimen position. Microsc. Microanal. 9, 1182–1183 (2003).
  108. ADS MATH  Google Scholar 
  109. Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
  110. CAS PubMed PubMed Central MATH  Google Scholar 
  111. Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
  112. CAS PubMed  Google Scholar 
  113. Asarnow, D., Palovcak, E. & Cheng, Y. asarnow/pyem: UCSF Pyem v0.5. Zenodo https://doi.org/10.5281/zenodo.3576630 (2019).
  114. Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
  115. CAS PubMed MATH  Google Scholar 
  116. Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).
  117. CAS PubMed PubMed Central MATH  Google Scholar 
  118. Bushdid, C., de March, C. A., Matsunami, H. & Golebiowski, J. Numerical models and in vitro assays to study odorant receptors. Methods Mol. Biol. 1820, 77–93 (2018).
  119. CAS PubMed  Google Scholar 
  120. Zhang, Y., Pan, Y., Matsunami, H. & Zhuang, H. Live-cell measurement of odorant receptor activation using a real-time cAMP assay. J. Vis. Exp. 128, 55831 (2017).
  121. Google Scholar 
  122. Berendsen, H. J. C., van der Spoel, D. & van Drunen, R. GROMACS: a message-passing parallel molecular dynamics implementation. Comput. Phys. Commun. 91, 43–56 (1995).
  123. ADS CAS  Google Scholar 
  124. Huang, J. et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat. Methods 14, 71–73 (2017).
  125. CAS PubMed MATH  Google Scholar 
  126. Vanommeslaeghe, K. et al. CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J. Comput. Chem. 31, 671–690 (2010).
  127. CAS PubMed PubMed Central  Google Scholar 
  128. Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).
  129. CAS PubMed  Google Scholar 
  130. Jo, S., Lim, J. B., Klauda, J. B. & Im, W. CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes. Biophys. J. 97, 50–58 (2009).
  131. ADS CAS PubMed PubMed Central  Google Scholar 
  132. Lomize, M. A., Pogozheva, I. D., Joo, H., Mosberg, H. I. & Lomize, A. L. OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res. 40, D370–D376 (2012).
  133. CAS PubMed  Google Scholar 
  134. Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: a new molecular dynamics method. J. Appl. Phys. 52, 7182–7190 (1981).
  135. ADS CAS MATH  Google Scholar 
  136. Darden, T., York, D. & Pedersen, L. Particle mesh Ewald: an N⋅log(N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089–10092 (1993).
  137. ADS CAS MATH  Google Scholar 
  138. Pagès, H., Aboyoun, P., Gentleman, R. & DebRoy, S. Biostrings: Efficient manipulation of biological strings. R package version 2.72.1 https://bioconductor.org/packages/Biostrings (2022).
  139. Charif, D. & Lobry, J. R. in Structural Approaches to Sequence Evolution: Molecules, Networks, Populations (eds Bastolla, U. et al.) 207–232 (Springer Berlin Heidelberg, 2007).
  140. Paradis, E. & Schliep, K. ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R. Bioinformatics 35, 526–528 (2019).
  141. CAS PubMed MATH  Google Scholar 
  142. Xu, S. et al. Ggtree: a serialized data object for visualization of a phylogenetic tree and annotation data. iMeta 1, e56 (2022).
  143. PubMed PubMed Central MATH  Google Scholar 
  144. Crooks, G. E., Hon, G., Chandonia, J.-M. & Brenner, S. E. WebLogo: a sequence logo generator. Genome Res. 14, 1188–1190 (2004).
  145. CAS PubMed PubMed Central  Google Scholar 
  146. Dang, S. et al. Cryo-EM structures of the TMEM16A calcium-activated chloride channel. Nature 552, 426–429 (2017).
  147. ADS CAS PubMed PubMed Central MATH  Google Scholar 

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