Why some like it spicy?

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Think Gene points me to a new PNAS paper, Structure of TRPV1 channel revealed by electron cryomicroscopy:

The transient receptor potential (TRP) family of ion channels participate in many signaling pathways. TRPV1 functions as a molecular integrator of noxious stimuli, including heat, low pH, and chemical ligands. Here, we report the 3D structure of full-length rat TRPV1 channel expressed in the yeast Saccharomyces cerevisiae and purified by immunoaffinity chromatography. We demonstrate that the recombinant purified TRPV1 channel retains its structural and functional integrity and is suitable for structural analysis. The 19-A structure of TRPV1 determined by using single-particle electron cryomicroscopy exhibits fourfold symmetry and comprises two distinct regions: a large open basket-like domain, likely corresponding to the cytoplasmic N- and C-terminal portions, and a more compact domain, corresponding to the transmembrane portion. The assignment of transmembrane and cytoplasmic regions was supported by fitting crystal structures of the structurally homologous Kv1.2 channel and isolated TRPV1 ankyrin repeats into the TRPV1 structure.

Think Gene and Scientific Blogging have summaries of the paper. Proteins are great, but what about the genes which produce them? I went to haplotter, and check out what I found….

iHS

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Screenshot of genes around TRPV1

Also check out variation around that gene.

Related: Genetics of taste.

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3 Comments

  1. 1- After much fumbling, I understood that these graphs indicate the value of various “measures of selection” at a given locus. CEU are Europeans, ASN are Asians, and YRI are Western Africans.  
     
    2- Judging from the graph, the “epicenter” of this sweeping area does not lie on TRPV1 but on the neighbouring TAX1BP3 and P2RX5. Those seem to be low-level genes involved in a lot of different physiological processes (especially the latter). Perhaps better informed people can suggest a possible selective pressure to explain this.

  2. That paper is rather interesting, but only a small step in the right direction. This quote  
     
    “With this first structure we can start to build models of binding sites and hopefully in the future design more effective pharmaceuticals for a wide range of medical conditions.? 
     
    is nothing but hype at this point–anything even approaching the resolution necessary for drug design is going to need a resolution at least 6 times better than the current one. This will require a completely different technique, like x-ray diffraction or NMR, that will in turn bring a whole new set of challenges. For now, models based on existing high-resolution structures of other ion channels are almost certainly of more use–including for the purpose of rationalizing the effect of mutations in the sequence.

  3. 1- After much fumbling, I understood that these graphs indicate the value of various “measures of selection” at a given locus. CEU are Europeans, ASN are Asians, and YRI are Western Africans.  
     
    CEU are Utah whites (mostly of self-reported British/Scandinavian ancestry as per US census). I don’t remember what the other two samples stand for but yes they attempt to represent Asians and Africans somewhat.  
     
    … 
     
    “With this first structure we can start to build models of binding sites and hopefully in the future design more effective pharmaceuticals for a wide range of medical conditions.? 
     
    is nothing but hype at this point
     
     
    They have to justify their salaries. It seems that science is more valuable if it has a technological potential, even if improbable, medical or pharmacological are the more plausible pretexts in the case of genetics.  
     
    Science for the sake of it may not be of the like of those who approve the budgets, you know.

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