scholarly journals Olfactory receptors are sensitive to molecular volume of odorants

2015 ◽  
Author(s):  
Majid Saberi ◽  
Hamed Seyed-allaei
Keyword(s):  
Olfactory Receptor ◽  
Experimental Studies ◽  
Chemical Properties ◽  
Olfactory Receptors ◽  
Binding Pocket ◽  
Olfactory Receptor Neuron ◽  
Neural Response ◽  
Molecular Volume ◽  
Combinatorial Encoding ◽  
Two Parameters

To study olfaction,
 first we should know which physical or chemical properties of odorant molecules determine 
 the response of olfactory receptor neurons, 
 and then we should study the effect of those properties on the combinatorial encoding in olfactory system.
 
 In this work we show that the response of an olfactory receptor neuron in Drosophila depends on molecular volume of an odorant; 
 The molecular volume determines the upper limits of the neural response, 
 while the actual neural response may depend on other properties of the molecules.
 Each olfactory receptor prefers a particular volume, 
 with some degree of flexibility.
 These two parameters predict the volume and flexibility of the binding-pocket of the olfactory receptors, 
 which are the targets of structural biology studies. 
 
 At the end we argue that the molecular volume can affects the quality of perceived smell of an odorant via the combinatorial encoding,
 molecular volume may mask other underlying relations between properties of molecules and neural responses 
 and we suggest a way to improve the selection of odorants in further experimental studies.

scholarly journals Molecular reconstruction of recurrent evolutionary switching in olfactory receptor specificity

2021 ◽  
Author(s):  
Lucia L. Prieto-Godino ◽  
Hayden R. Schmidt ◽  
Richard Benton
Keyword(s):  
Ligand Binding ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Binding Pocket ◽  
Amino Acid Identity ◽  
Major Effect ◽  
Ligand Docking ◽  
Ionotropic Receptor ◽  
Ligand Binding Pocket ◽  
Receptor Interactions

AbstractOlfactory receptor repertoires exhibit remarkable functional diversity, but how these proteins have evolved is poorly understood. Through analysis of extant and ancestrally-reconstructed drosophilid olfactory receptors from the Ionotropic Receptor (IR) family, we investigated evolution of two organic acid-sensing receptors, IR75a and IR75b. Despite their low amino acid identity, we identify a common “hotspot” in their ligand-binding pocket that has a major effect on changing the specificity of both IRs, as well as at least two distinct functional transitions in IR75a during evolution. Ligand-docking into IR models predicts that the hotspot does not contact odor molecules, suggesting that this residue indirectly influences ligand/receptor interactions. Moreover, we show that odor specificity is refined by changes in additional, receptor-specific sites, including those outside the ligand-binding pocket. Our work reveals how a core, common determinant of ligand-tuning acts within epistatic and allosteric networks of substitutions to lead to functional evolution of olfactory receptors.

scholarly journals Molecular reconstruction of recurrent evolutionary switching in olfactory receptor specificity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Lucia L Prieto-Godino ◽  
Hayden R Schmidt ◽  
Richard Benton
Keyword(s):  
Ligand Binding ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Binding Pocket ◽  
Amino Acid Identity ◽  
Major Effect ◽  
Receptor Specificity ◽  
Ionotropic Receptor ◽  
Ligand Binding Pocket ◽  
Acid Identity

Olfactory receptor repertoires exhibit remarkable functional diversity, but how these proteins have evolved is poorly understood. Through analysis of extant and ancestrally-reconstructed drosophilid olfactory receptors from the Ionotropic receptor (Ir) family, we investigated evolution of two organic acid-sensing receptors, Ir75a and Ir75b. Despite their low amino acid identity, we identify a common 'hotspot' in their ligand-binding pocket that has a major effect on changing the specificity of both Irs, as well as at least two distinct functional transitions in Ir75a during evolution. Moreover, we show that odor specificity is refined by changes in additional, receptor-specific sites, including those outside the ligand-binding pocket. Our work reveals how a core, common determinant of ligand-tuning acts within epistatic and allosteric networks of substitutions to lead to functional evolution of olfactory receptors.

scholarly journals The structural basis of odorant recognition in insect olfactory receptors

Nature ◽  
2021 ◽  
Author(s):  
Josefina del Mármol ◽  
Mackenzie A. Yedlin ◽  
Vanessa Ruta
Keyword(s):  
Olfactory Receptor ◽  
Hydrophobic Interactions ◽  
Olfactory Receptors ◽  
Binding Pocket ◽  
Structural Basis ◽  
Structural Determinants ◽  
Cryo Electron Microscopy ◽  
Common Strategy ◽  
Olfactory Systems ◽  
Discriminatory Capacity

AbstractOlfactory systems must detect and discriminate amongst an enormous variety of odorants1. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors1–3, thus allowing a finite number of receptors to detect a vast chemical world. Here we offer structural and mechanistic insight into how an individual olfactory receptor can flexibly recognize diverse odorants. We show that the olfactory receptor MhOR5 from the jumping bristletail4Machilis hrabei assembles as a homotetrameric odorant-gated ion channel with broad chemical tuning. Using cryo-electron microscopy, we elucidated the structure of MhOR5 in multiple gating states, alone and in complex with two of its agonists—the odorant eugenol and the insect repellent DEET. Both ligands are recognized through distributed hydrophobic interactions within the same geometrically simple binding pocket located in the transmembrane region of each subunit, suggesting a structural logic for the promiscuous chemical sensitivity of this receptor. Mutation of individual residues lining the binding pocket predictably altered the sensitivity of MhOR5 to eugenol and DEET and broadly reconfigured the receptor’s tuning. Together, our data support a model in which diverse odorants share the same structural determinants for binding, shedding light on the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.

scholarly journals Molecular Modelling of Oligomeric States of DmOR83b, an Olfactory Receptor in D. Melanogaster

2012 ◽  
Vol 6 ◽  
pp. BBI.S8990 ◽  
Author(s):  
K. Harini ◽  
R. Sowdhamini
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Insect Species ◽  
Agricultural Pests ◽  
Negative Effects ◽  
C Terminus ◽  
Receptor Neurons ◽  
Medical Importance ◽  
G Protein Coupled ◽  
Made In

After the discovery of the complete repertoire of D. melanogaster Olfactory Receptors (ORs), candidate ORs have been identified from at least 12 insect species from four orders (Coleoptera, Lepidoptera, Diptera, and Hymenoptera), including species of economic or medical importance. Although all ORs share the same G-protein coupled receptor structure with seven transmembrane domains, they share poor sequence identity within and between species, and have been identified mainly through genomic data analyses. To date, D. melanogaster remains the only insect species where ORs have been extensively studied, from expression pattern establishment to functional investigations. These studies have confirmed several observations made in vertebrates: one OR type is selectively expressed in a subtype of olfactory receptor neurons, and one olfactory neuron expresses only one type of OR. The olfactory mechanism, further, appears to be conserved between insects and vertebrates. Understanding the function of insect ORs will greatly contribute to the understanding of insect chemical communication mechanisms, particularly with agricultural pests and disease vectors, and could result in future strategies to reduce their negative effects. In this study, we propose molecular models for insect olfactory receptor co-receptor OR83b and its possible functional oligomeric states. The functional similarity of OR83b to GPCRs and ion channels has been exploited for understanding the structure of OR83b. We could observe that C-terminal region (TM4-7) of OR83b is involved in homodimer amd heterodimer formation (with OR22a) which suggests why C-terminus of insect ORs are highly conserved across different species. We also propose two possible ion channel pathways in OR83b: one formed by TM4-5 region with intracellular pore-forming domain and the other formed by TM5-6 with extracellular pore forming domain using analysis of the electrostatics distribution of the pore forming domain.

scholarly journals In Silico Screening for Natural Ligands to Non-Structural Nsp7 Conformers of Coronaviruses

2020 ◽  
Author(s):  
Rafael Blasco ◽  
Julio Coll
Keyword(s):  
In Silico ◽  
Chemical Properties ◽  
Structural Similarity ◽  
Binding Pocket ◽  
Binding Affinities ◽  
Structural Protein ◽  
Autodock Vina ◽  
Natural Ligands ◽  
Final Optimization

<p>The non-structural protein 7 (nsp7) of Severe Acute Respiratory Syndrome (SARS) coronaviruses was selected as a new target to potentially interfere with viral replication. The nsp7s are one of the most conserved, unique and small coronavirus proteins having a critical, yet intriguing participation on the replication of the long viral RNA genome after complexing with nsp8 and nsp12. Despite the difficulties of having no previous binding pocket, two high-throughput virtual blind screening of 158240 natural compounds > 400 Da by AutoDock Vina against nsp7.1ysy identified 655 leads displaying predicted binding affinities between 10 to 1100 nM. The leads were then screened against 14 available conformations of nsp7 by both AutoDock Vina and seeSAR programs employing different binding score algorithms, to identify 20 consensus top-leads. Further <i>in silico</i> predictive analysis of physiological and toxicity ADMET criteria (chemical properties, adsorption, metabolism, toxicity) narrowed top-leads to a few drug-like ligands many of them showing steroid-like structures. A final optimization by search for structural similarity to the top drug-like ligand that were also commercially available, yielded a collection of predicted novel ligands with ~100-fold higher-affinity whose antiviral activity may be experimentally validated. Additionally, these novel nsp7-interacting ligands and/or their further optimized derivatives, may offer new tools to investigate the intriguing role of nsp7 on replication of coronaviruses.</p>

scholarly journals Organization and distribution of glomeruli in the bowhead whale olfactory bulb

2014 ◽  
Author(s):  
Takushi Kishida ◽  
J. G. M. Thewissen ◽  
Sharon Usip ◽  
John C George ◽  
Robert S Suydam
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Molecular Data ◽  
Dorsal Side ◽  
Bowhead Whale ◽  
Model Organisms ◽  
Marker Genes ◽  
Baleen Whales ◽  
Olfactory Receptor Genes

Although modern baleen whales still possess a functional olfactory systems that includes olfactory bulbs, cranial nerve I and olfactory receptor genes, their olfactory capabilities have been reduced profoundly. This is probably in response to their fully aquatic lifestyle. The glomeruli that occur in the olfactory bulb can be divided into two non-overlapping domains, a dorsal domain and a ventral domain. Recent molecular studies revealed that all modern whales have lost olfactory receptor genes and marker genes that are specific to the dorsal domain, and that a modern baleen whale possess only 60 olfactory receptor genes. Here we show that olfactory bulb of bowhead whales (Balaena mysticetus, Mysticeti) lacks glomeruli on the dorsal side, consistent with the molecular data. In addition, we estimate that there are more than 4,000 glomeruli in the bowhead whale olfactory bulb. Olfactory sensory neurons that express the same olfactory receptor in mice generally project to two specific glomeruli in an olfactory bulb, meaning that ratio of the number of olfactory receptors : the number of glomeruli is approximately 1:2. However, we show here that this ratio is not applicable to whales, indicating the limitation of mice as model organisms for understanding the initial coding of odor information among mammals.

On the regular growth of soluble salts on each other

1907 ◽  
Vol 14 (66) ◽  
pp. 235-257 ◽  
Author(s):  
Thomas Vipond Barker
Keyword(s):  
Chemical Properties ◽  
Reasonable Doubt ◽  
Regular Growth ◽  
Molecular Volume ◽  
Soluble Salts

Previous work on the regular growth of crystals of salts on those of Minerals belonging to the same isostructural series led the author to the discovery that parallel deposition is conditioned by closeness, not of angle nor of axial ratios, but of molecular volume. Now although the substances previously examined resemble each other crystallographically, yet they exhibit such great differences in chemical properties, that reasonable doubt might be entertained whether conclusions drawn from them can be directly applied to isomorphous substances ; and it therefore became advisable to extend the observations to a group of the latter.

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