They even made a film about its water channel from the cytosolic proton source to the central horizontal transfer zone, and it's available in the supplementary data to down load:
I had to look very carefully in slo-mo, advancing the frames manually, at some points one by one, to work out what is happening. It's simpler if you edit out the (undoubtedly very important) shuffling of hydrogen bonds to the isoleucine on the right hand side of the image. I've made a simplified gif of the track of the proton from bulk solvent at the top to where it protonates the glutamate at the bottom. This is only a half-channel, quite where the second half-channel is located is unclear but there are several possibilities discussed. Here's the grossly simplified gif with the proton highlighted in blue and the shuffling of hydrogen bonds to the isoleucine cut out:
We can summarise this as a proton from bulk solvent:
"travels" to a "half way" glutamate and protonates it, which reconfigures the proteins to expel the water molecules and so closes the input side of the channel:
Now let's speculate wildly, as you do. Next comes the "kick" from the doohickey in the redox arm and transmitted through NuoH (or Nqo8 in bacteria):
There is a convenient lysine to accept it. Tucked in behind the lysine is another glutamate which can next be protonated:
to open the water channel to the periplasm
and complete the transfer to the 4th proton:
This fourth channel is messy. Nuos N, M and L are clearly lifted straight from the MRP antiporter as complete units. The above pathway is a hotchpotch of one edge of Nuo N and the small membrane subunits Nuos A, J and K. If you had to guess, these small subunits might be remnants of the Na+ channel of the MRP antiporter but I've not seen this hypothesised anywhere.
I'll pause here because the principle of water wires and proton transfer appears to be very generic, the three tidy channels will be functionally very similar to the messy fourth channel described here.
Unlike NuoH. That's the next post. It's totally different.
Peter
4 comments:
Meanwhile, over in Clown World, scientist have discovered that meat eaters are guilty of higher CO2 exhalation than vegetarians, among other things.
'Scientists Discover Animals Breathe' https://wmbriggs.substack.com/p/scientists-discover-animals-breathe
Vegans, while farting: LOOK! That meat-eater!!!! HE’S BREATHING!!!! THE HORROR!!!!! 🤡
Peter, I think that their animation looks like the proton hopping one here:
https://en.wikipedia.org/wiki/Grotthuss_mechanism
(obviously without the additional mechanics, but still!)
Also,
"In his 1806 publication “Theory of decomposition of liquids by electrical currents”, Theodor Grotthuss proposed a theory of water conductivity.[1] Grotthuss envisioned the electrolytic reaction as a sort of ‘bucket line’ where each oxygen atom simultaneously passes and receives a single hydrogen ion. It was an astonishing theory to propose at the time, since the water molecule was thought to be OH not H2O and the existence of ions was not fully understood. On its 200th anniversary, his article was reviewed by Cukierman.[2]
Although Grotthuss was using an incorrect empirical formula of water, his description of the passing of protons through the cooperation of neighboring water molecules proved prescient."
In 1806. Mind blown.
If nothing else, thank you yet again for making me find awesome things like this!
These posts are fascinating, however little I understand of them.
But! I have a DNA sample in the mail for a study on monogenic diabetes, and on tenterhooks for those test results. If I can find out what kind of mutants my family are, that will open a whole new window on this metabolism thing, and I will be coming back here to comb through these posts and see if I can play match-the-function. Fingers crossed.
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