[HN Gopher] Secret Workings of Smell Receptors Revealed for Firs...
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       Secret Workings of Smell Receptors Revealed for First Time
        
       Author : pseudolus
       Score  : 51 points
       Date   : 2021-06-22 10:30 UTC (1 days ago)
        
 (HTM) web link (www.quantamagazine.org)
 (TXT) w3m dump (www.quantamagazine.org)
        
       | monkeybutton wrote:
       | Very interesting! I remember this being an odd gap when I took an
       | introduction to neuroscience course many years ago. Visual
       | perception was well understood, auditory was fairly complete
       | (although I remember there being some mystery around sound
       | frequencies that are to fast to be encoded), and then smell was
       | "We have some idea but its complex and not like the others. Some
       | theories may involve quantum mechanics".
        
       | post_break wrote:
       | I wish we knew more on how covid messed them up and how to fix.
       | Ever since I had covid my smell sensitivity is very low. I get
       | really weird smells and tastes from food that sometimes make me
       | sick.
        
         | burnished wrote:
         | If I understand correctly[1] covid messes with supporting cells
         | and not the sensory neurons themselves and there is hope that
         | this means that particular side effect should be temporary.
         | 
         | [1]https://hms.harvard.edu/news/how-covid-19-causes-loss-smell
        
       | UncleOxidant wrote:
       | 'Secret' doesn't seem like the right word to use here. It implies
       | that it was some sort of government coverup.
        
         | SllX wrote:
         | 'Secret' in context here simply refers to a mystery, much like
         | "secrets of the Universe" would.
        
       | favoritecolor wrote:
       | I love when I see smell research on Hacker News -- and hopefully
       | I can provide a bit of context about this paper.
       | 
       | This finding recently made a big splash at AChemS 2021 (the
       | annual meeting for the Association for Chemoreception Sciences).
       | And it actually is a really big deal. A protein structure is
       | extremely information rich, telling you where all of the atoms of
       | a given protein are (ish). Before this finding, there were NO
       | structures of any olfactory receptor, and historically the
       | publication of the first structure of a given biomolecule has
       | been a watershed moment for that field (insulin, ribosome, many
       | other examples).
       | 
       | What's more, they used the structural information to rationally
       | engineer their olfactory receptor, expanding the binding pocket
       | and changing how the receptor responds to different odorants.
       | That was pretty much impossible to do before this. So, this is a
       | pretty huge finding, and will definitely encourage more
       | structural work on olfactory receptors in the future.
       | 
       | If I had to poke a hole in this finding, it would be that insect
       | olfactory receptors are substantially different from mammalian
       | olfactory receptors. But in my opinion, it seems that the buzz
       | about this paper is definitely justified. Very cool!
        
         | shoto_io wrote:
         | Is this in any way support for the "Vibration theory of
         | olfaction"?
         | 
         | https://en.wikipedia.org/wiki/Vibration_theory_of_olfaction
        
           | beebeepka wrote:
           | Thanks to your link, I discovered this:
           | https://en.m.wikipedia.org/wiki/Docking_theory_of_olfaction
           | 
           | Had no idea it's just a theory. I've lived many years
           | "knowing" that we detect smells due to their shapes.
        
             | Duller-Finite wrote:
             | This paper is the first structure of any odorant receptor-
             | ligand interaction. There's currently no equivalent
             | structure for mammalian odorant receptors to validate the
             | docking theory, but it's likely correct.
        
         | [deleted]
        
         | jfengel wrote:
         | Question: does this put an end to Luca Turin's vibration
         | theory?
         | 
         | I realize that this has long been considered crackpottery, and
         | there has never been a reasonable sense of a mechanism for it.
         | But it did seem to offer at least a stab at a couple of
         | questions that didn't have good answers in the ordinary lock-
         | and-key model of olfaction, such as why sulfur-containing
         | molecules all smell "sulfury" if they all unlock different
         | locks.
         | 
         | As far as I can tell the idea sorta just died out. A lot of
         | work was done trying to make odor molecules with different
         | isotopes, with intriguing but inconclusive results.
         | 
         | Still, I've been kinda curious to see if the theory was finally
         | over and done.
        
       | smegcicle wrote:
       | about time we start working on the smell-o-vision future
       | predicted in the 6G whitepaper from the international telegraph
       | union
       | 
       | https://www.itu.int/en/ITU-T/focusgroups/net2030/Documents/W...
        
       | Duller-Finite wrote:
       | This is truly a landmark study. This is the first structure of
       | any odorant receptor. It is, however, one from an insect, so the
       | structure is not homologous to mammalian olfactory receptors,
       | which are a large family of G-protein-coupled receptors.
        
         | epmaybe wrote:
         | Forgive my ignorance, but I am wondering if this is all that
         | different. GPCRs typically downstream towards ion channels,
         | right? So even if insect physiology relies on ligand gated ion
         | channels, is the end result the same, just more metabolically
         | expensive in mammals?
        
           | Duller-Finite wrote:
           | Not really. GPCRs amplify signals at each step via their
           | second messenger cascade. These channels form homotetramers
           | whose structure differs greatly from the canonical seven
           | transmembrane domain structure of GPCRs. So this study is
           | important since there were no studies indicating how odorants
           | bind and activate odorant receptors. However, it is unlikely
           | that the mechanisms in insects odorant receptors will
           | directly apply to those of mammalian odorant receptors. In
           | contrast, mammalian odor receptors will work much more like
           | those of other class A GPCRs like the b-adrenergic receptor,
           | of which there are numerous structures interacting with
           | ligands and in various configurations, and which was the
           | basis of the work that won the nobel prize in 2012.
        
       | amelius wrote:
       | I'm smelling click-bait.
        
         | Uhhrrr wrote:
         | Reasonable, given the title, but as someone who had no idea how
         | smell receptors work, I thought it was neat.
         | 
         | The nut:
         | 
         | > [T]he limited repertoire of receptors on its olfactory
         | sensory neurons must somehow recognize a vast number of
         | compounds. So an individual receptor has to be able to respond
         | to many diverse, seemingly unrelated odor molecules.
         | 
         | > That versatility is at odds with the traditional lock-and-key
         | model governing how selective chemical interactions tend to
         | work. [....]
         | 
         | > Now, new work has taken a crucial and much anticipated step
         | forward in elucidating the beginning stages of the olfactory
         | process. In a preprint posted online earlier this year, a team
         | of researchers at Rockefeller University in New York provided
         | the first molecular view of an olfactory receptor as it bound
         | to an odor molecule.
        
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       (page generated 2021-06-23 23:01 UTC)