Structural basis of odorant recognition by a human odorant receptor
Christian B. BillesbølleClaire A. de MarchWijnand J. C. van der VeldenNing MaJeevan TewariClaudia Llinás del TorrentLinus LiBryan FaustNagarajan VaidehiHiroaki MatsunamiAashish Manglik
4
Citation
69
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Our sense of smell enables us to navigate a vast space of chemically diverse odor molecules. This task is accomplished by the combinatorial activation of approximately 400 olfactory G protein-coupled receptors (GPCRs) encoded in the human genome 1–3 . How odorants are recognized by olfactory receptors (ORs) remains mysterious. Here we provide mechanistic insight into how an odorant binds a human olfactory receptor. Using cryogenic electron microscopy (cryo-EM), we determined the structure of active human OR51E2 bound to the fatty acid propionate. Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation. Mutation of the odorant binding pocket in OR51E2 alters the recognition spectrum for fatty acids of varying chain length, suggesting that odorant selectivity is controlled by tight packing interactions between an odorant and an olfactory receptor. Molecular dynamics simulations demonstrate propionate-induced conformational changes in extracellular loop 3 to activate OR51E2. Together, our studies provide a high-resolution view of chemical recognition of an odorant by a vertebrate OR, providing insight into how this large family of GPCRs enables our olfactory sense.Objectives Olfaction is frequently impaired in chronic rhinosinusitis with nasal polyps (CRSwNP) and often improves after endoscopic sinus surgery (ESS). Data about dynamics of olfactory changes after ESS are lacking, and little information is available concerning whether preoperatively administered glucocorticosteroids predict postoperative olfaction. Therefore, the aim of this study was to examine dynamics of olfaction after ESS in relation to the effect of preoperative administration of glucocorticosteroids in CRSwNP. Methods This prospective study included 52 CRSwNP patients (30 men, 22 women, mean age 54 ± 14 years) divided into a control group (n = 31) subjected to ESS without preoperative steroids and a treatment group (n = 21) receiving orally administered glucocorticosteroids preoperatively. Self‐ratings of olfaction and olfactory testing using the extended Sniffin’ Sticks test battery (threshold, discrimination and identification [TDI] score) were performed. Olfaction was measured preoperatively; after termination of glucocorticosteroid treatment (only treatment group); and 2 weeks, 1 month, and 3 months postoperatively. Results After glucocorticosteroids, TDI score significantly improved in 57% of patients, and olfactory function remained unchanged in 43%. In addition, improvement in TDI score after steroids and 3 months postoperatively were significantly correlated (r = 0.66, P = 0.01). Patients whose olfaction did not improve after glucocorticosteroids did not benefit from surgery. Regarding postoperative olfactory dynamics, TDI score reached its maximum 1 month postoperatively and decreased again approximately 3 months after surgery. Conclusion Glucocorticosteroids improved olfaction in CRSwNP comparable to surgery. In addition, changes in relation to steroids predicted olfactory outcome postoperatively. Regarding the olfactory dynamics, it could be demonstrated that olfactory function increased 1 month after surgery and decreased 3 months postoperatively. Level of Evidence 2 Laryngoscope , 130:1616–1621, 2020
Chronic Rhinosinusitis
Endoscopic sinus surgery
Cite
Citations (18)
Section:ChooseTop of pageAbstract <
Sensation
Cite
Citations (92)
Trigeminal Nerve
Olfactory nerve
Cite
Citations (195)
Human brain
Cite
Citations (39)
Neuromorphic engineering
Antennal lobe
Olfactory nerve
Cite
Citations (0)
Abstract Olfactory dysfunction (OD) in Parkinson’s disease (PD) appears several years before the presence of motor disturbance. Olfactory testing has the potential to serve as a tool for early detection of PD, but OD is not specific to PD as it affects up to 20% of the general population. Olfaction includes an orthonasal and a retronasal components; in some forms of OD, retronasal olfactory function is preserved. We aimed to evaluate whether combined testing components allows for discriminating between PD-related OD and non-Parkinsonian OD (NPOD). The objective of this study is to orthonasal and retronasal olfactory function in PD patients and compare them to a NPOD group and to healthy controls. We hypothesized that this combined testing allows to distinguish PD patients from both other groups. We included 32 PD patients, 25 NPOD patients, and 15 healthy controls. Both olfactory components were impaired in PD and NPOD patients, compared with controls; however, NPOD patients had significantly better orthonasal scores than PD patients. Furthermore, the ratio of retronasal/orthonasal score was higher in PD than in both other groups. In the NPOD group, orthonasal and retronasal scores were significantly correlated; no such correlation could be observed in PD patients. In summary, PD patients seem to rely on compensatory mechanisms for flavor perception. Combined orthonasal and retronasal olfactory testing may contribute to differentiate PD patients from patients with NPOD.
Hyposmia
Cite
Citations (10)
Hyposmia
Anosmia
Cite
Citations (5)
The pre- and postnatal development of human olfaction is described. Data from animal experiments a partially reviewed as a base for understanding of the results of olfactory testing of babies and children. In rat fetuses the vomero-nasal-organ is used as detector of molecules in the amnion fluid. The perinatal aeration of the nasal cavity allows the adequate stimulation of the olfactory epithelium. The early postnatal olfaction is a brainstem function; later the olfactory cortical area are used for the discrimination between odorants. There are only a few investigations about the olfactory function in childhood, so that the testing of olfaction for detecting abnormal brain developments is just in the beginning.
Olfactory mucosa
Cite
Citations (2)
The olfaction is related to flow in the olfactory cleft. However, There is a lack of studies on the relationship between flow characteristics of the olfactory cleft and olfactory function. In this study, the anatomical structure of the olfactory cleft was reconstructed in three dimensions using the raw data obtained from the CT scans of sinuses of 32 enrolled volunteers. The Sniffin' Sticks test was used to examine the olfaction. We investigated the correlation between airflow parameters and olfactory function of the olfactory cleft in healthy adults by the computational fluid dynamics method. We found that three parameters, airflow, airflow velocity, and airflow ratio, were highly positively correlated with olfactory function. The mean pressure was not correlated with the olfactory function. Furthermore, there is the strongest correlation between air flow through the olfactory cleft and olfactory function. The correlation between the mean velocity in the anterior olfactory cleft region and olfaction was relatively poor, while the airflow velocity at the posterior olfactory cleft region was enhanced gradually. The correlation between the airflow ratio and olfaction was optimal in the initial position of superior turbinate. The flow parameters in the posterior olfactory cleft area were more stable.
Cite
Citations (6)