Tag Archives: Single letter amino acid code

A science fiction story (for the cognoscenti) — answer to the puzzle and a bit more

Comrade Chen we have a serious problem.

Don’t tell me one of our bugs escaped confinement.

Worse.  One of theirs did.  And it’s affecting the PLA (People’s Liberation Army).  Some are turning into pacifists.

It doesn’t kill them?

No. But for our purposes it might as well.

It’s a typical adenoassociated virus (AAV) like we use.

Well, what does the genome look like?

We’ve sequenced it and among other things, it codes for a protein which enters the brain and alters behavior.

What?

Well, the enemy has some excellent biologists, one of whom works on Wolbachia.

What’s that?

It’s a rickettsial organism which changes the sex life of some insects.

I don’t believe that.

Do you have a cat?

Yes.

Well many cats contain another organism (toxoplasma gondi).

So what.

Rats infected by the organism become less afraid of cats.

Another example please.

A fungus infecting carpenter ants causes the ant to leave its colony, climb a tree, chomp down on the underside of a leaf and die, freeing fungal spores to fall on the ground where they can reinfect new ants.

Well what is the genome of the virus?

It has some very unusual sequences, and one which proves that the Wolbachia biologist on the other side has a very large ego.

How so.

Well in addition to the brain infecting protein, there is a very unusual triplet of peptides all in a row.

Methionine Alanine Aspartic Acid Glutamic acid, then a stop codon, then Isoleucine Asparagine, than a stop codon, then Threonine Alanine Isoleucine Tryptophan Alanine Asparagine.  We think that the first two in some way cause readthrough of the stop codons so the protein following the short peptides is made.

Where does the big ego come in?

Sir, proteins can have hundreds and hundreds of amino acids.  People got tired of writing their full names out, so each of the 20 amino acids was given a single letter to stand for it.

M – Methionine

A – Alanine

D – Aspartic acid

What does D have to do with Aspartic acid?

Nothing sir, look on the letters as Chinese characters.

E -Glutamic Acid

I – isoleucine

What about the stop codon between Glutamic acid and Isoleucine

Just regard it as a space.

N – Asparagine

Nooo! ! ! I I’m beginning to get the picture.

Yes sir, it stands for MADE IN TAIWAN

—-

A few years later

Well the Taiwanese biologist outsmarted himself (or herself).   The Taiwanese soldiers wouldn’t fight either as the virus spread.  Most conflicts between nation states pretty much ended (Russia/Ukraine, North Korea/South Korea) etc. etc.  The Taiwanese biologist was nominated for the Nobel Peace Prize, and did receive it in absentia, as every military type in the world was looking for him (or  her), so he (or she) went into hiding, and is believed to be living in an Ashram near Boulder, Colorado.

Unfortunately, the idea of using viruses to change human behavior spread past nation states, and private groups with their own agendas began using it.

The ‘new soviet man’ of the previous century looked rather benign compared to what subsequently happened.

The next story for the scientific cognoscenti will describe the events leading up to the impeachment trial of President Jon Tester in 2028.

 

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What are prions for?

Prions existed in yeast billions of years before humanity came on the scene. Why are they still there? What are they for?  Immediately we are back in the Aristotelian world of teleology, where everything had a reason for existence and a purpose.  http://www.sparknotes.com/philosophy/aristotle/themes.html.  Teleology is simply impossible to avoid in biology. “Nothing in Biology Makes Sense Except in the Light of Evolution” is a famous quote from the magnificently named Theodosius Dobzhansky, which clothes naked teleology with respectable scientific garments.

Here’s an example of this sort of thing from back in the day.  When I was back in the Denver VA as a neurology resident dealing with the complications of immunosuppressants in Starzl’s early work on transplantation, we wondered what on earth the transplantation antigens were for.  All we knew then, is that they were important in transplant rejection. Surely they were not there to prevent cells of the same or another species from finding a new home in us.  Only later did we figure out that they were involved in antigen presentation.

A fascinating article from the first Science of the new year — http://science.sciencemag.org/content/359/6371/eaao5654 describes how the yeast organism might be using one of them (Sup35) — e.g. what the prion domains are for.  Normally the Sup35 protein functions to terminate messenger RNA (mRNA) translation into protein. However the first 123 amino acids of Sup35 can aggregate forming amyloid fibrils.  It contains a series of 9 amino acid repeats with consensus sequence PQGGYQQYN (single letter amino acid code — http://130.88.97.239/bioactivity/aacodefrm.html) which is similar to the human prion protein repeats (PHGGGWGQ).

This work showed that under a variety of stesses (energy depletion, lowering of intracellular pH) Sup35 doesn’t form amyloid-like prions, but something rather different — liquidlike spherical condensates, which subsequently solidify to form a protein gel.  Next to the prion domain is a very acidic region, important in formation of the condensate.  Low pH is seen in energy depletion, and protonates the acidic amino acids in the acidic region leading to condensate formation.   A mutated Sup35 containing only the prion domain and the acidic region will form the condensates as well in a pH dependent manner.  The condensates are far from irreversible (like prions) as they quickly disappear when the pH is raised.

If you take out the prion domain from Sup35, the catalytic region (a GTPase) in the carboxy terminal part forms irreversible aggregates — so the prion domain is in some way preventing this.

So basically the two other parts of Sup35 function to protect the business end of Sup35 from being totally put out of commission by irreversible aggregation.

The authors found that yeast cells containing Sup35 lacking the prion domain, after recovering from stress, showed impaired translational activity and a growth defect presumably because there was less functional Sup35 around. This may be what the prion domain is doing.

My guess is that the aggregation of Sup35 into actual prions has a function in yeast that we just haven’t figured out yet.

It will be interesting to see if other yeast prions (there are many) show the similar behavior (condensate formation under stress).