Artificial Receptors Could Help Us Solve the Puzzle of Olfaction

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field--label-hidden">Artificial Receptors Could Help Us Solve the Puzzle of Olfaction</span> </h1> <h2 class="field field-sub-title field--type-text field--label-hidden article-header__subheading">Scent molecules “jiggle” inside of model olfactory receptors to activate them, revealing some of the molecular motions that create our sense of smell.</h2> <p class="article-header__author"> </p> </header> <ul class="article-meta-share"> <li><a rel="nofollow" href="https://www.facebook.com/share.php?u=https://www.ucsf.edu/news/2024/10/428766/artificial-receptors-could-help-us-solve-puzzle-olfaction" target="_blank" title="Share on Facebook"><span class="fab fa-facebook-square"></span> <span class="indent-text">Share on Facebook</span></a></li> <li><a rel="nofollow" href="https://www.twitter.com/share?text=Artificial Receptors Could Help Us Solve the Puzzle of Olfaction&url=https://www.ucsf.edu/news/2024/10/428766/artificial-receptors-could-help-us-solve-puzzle-olfaction" target="_blank" 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href="/cdn-cgi/l/email-protection#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" title="Email this article"><span class="fas fa-envelope-square"></span> <span class="indent-text">Email this article</span></a></li> <li><a rel="nofollow" onclick="window.print();return false;" href="https://www.ucsf.edu/news/2024/10/428766/artificial-receptors-could-help-us-solve-puzzle-olfaction" title="Print this article"><span class="fas fa-print"></span> <span class="indent-text">Print this article</span></a></li> </ul> <div class="page_narrow"><p>Our noses can effortlessly distinguish the aroma of coffee from the tang of gasoline, yet how they do it has long been a mystery.</p> <p>In a study that appears Oct. 30 in <em><a href="https://www.nature.com/articles/s41586-024-08126-0">Nature</a></em>, scientists at Duke University School of Medicine, UC San Francisco and City of Hope provide a glimpse into the complex mechanics that enable the nose to decode an astonishing range of odors with precision.</p> <p>The team designed four model receptors based on the shapes of the 400 odorant receptors (ORs), then took snapshots at atomic-level resolution as the receptors encountered scent molecules.</p> <p>“Every time you smell something like coffee or bread, you’re actually picking up hundreds of different odor molecules,” said co-senior author Hiro Matsunami, PhD, professor of molecular genetics and microbiology at Duke School of Medicine. “Our brain distinguishes various odors seamlessly, but understanding how that works at a molecular level has been a challenge.”</p> <p>The study focused on two main types of odorant receptors: Class I receptors, which are sensitive to cheese or vinegar-like smells, and Class II receptors, which are more versatile and pick up a wider range of scents.</p> <p>Real human receptors, however, were “impossible to make in a test tube,” precluding any detailed analysis of how they interacted with scents, explained Aashish Manglik, MD, PhD, professor of pharmaceutical chemistry in the UCSF School of Pharmacy and co-senior author of the paper.</p> <p>So, the team engineered four model ORs based on the structure of some of the major subtypes of the human OR to see how they worked.</p> <p>Advanced cryo-electron microscopy (cryo-EM) allowed the team to capture detailed 3D images of the model ORs as they detected scent molecules.</p> <p>To visualize how these receptors move and change with different odors, City of Hope scientists created computer simulations to model these movements.</p> <p>“This helps us understand how smell receptors recognize and respond to odors in real life,” said co-senior study author Nagarajan Vaidehi, PhD, professor and chair of the Department of Computational and Quantitative Medicine within Beckman Research Institute of City of Hope.</p> <h2>A loose fit between scent and receptor</h2> <p>Some receptors in the body work with the rigidity and precision of a lock: they are activated only when the corresponding molecular “keys” or engages with them.</p> <p>But the model ORs behaved differently.</p> <p>“The way these odor molecules bind these receptors is surprisingly dynamic and flexible – the key jiggles around in the lock quite a bit to open it,” Manglik said.</p> <p>This flexibility could help explain why individual ORs can sense so many different odorants.</p> <p>“During evolution, ORs had to diversify to detect ever-wider ranges of odorants,” said co-first author of the paper Claire de March, PhD, professor at the Université Paris-Saclay and former Duke researcher. “These model ORs are just the start for understanding olfaction.”</p> <p class="small-text"><strong>Additional authors:</strong> Ning Ma and Christian B. Billesbolle were also co-first authors of the paper. 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