I’m guessing the codon+ribosome changes the affinity of the molecule to be more accepting of a specific trna/amino acid? Do we know how exactly that happens though? Is my understanding of how it works correct at all?
Like, I know that uua codes for leucine, but there must be chemical properties that make it so, right?
We can try explaining like I’m 15, not 5 lol.
In: Biology
It all about relative chemical bond strength and probability. The “right” amino acid has a higher bond strength than the “wrong” amino acid, so it is much easier for the “right” amino acid to kick out a “wrong” amino acid than the other way around. The longer that the ribosome waits on a given slot, the more likely that the “right” amino acid will eventually show up and kick out any squatters. Note that this means that the number of protein translation errors is inversely proportional to how much time the ribosome waits at each “slot”. How long the ribosome waits seems to be regulated by the specific genetic sequence the ribosome is reading as if the ribosome has been preprogrammed to know which genetic sequences are more important and which ones are less important.
tRNA has a sequence of nucleotides called the anticodon that complements the codon, with some wobble in the third position. Same way any nucleotides base pair.
As u/JaceyLessThan3 said, the tRNA contains an anticodon, a three-nucleotide sequence which is complementary to the codon. When it binds to the ribosome, that sequence is positioned so that it contacts the codon on the mRNA, and if the base-pairing is correct the binding will be much tighter than if it is not. Note that this isn’t just about the binding energy of those three base pairs – the positioning of the tRNA will be different for complementary and non-complementary codon-anticodon pairs, and the ribosome makes other interactions with the tRNA that can detect those differences.
The key point here is that, as far as we know, the pairing between tRNA and amino acid is essentially arbitrary. The ribosome has no way to tell what amino acid is attached to the tRNA, it’s relying entirely on the anticodon to recognize what tRNA it’s binding; the amino-acid selectivity comes from the aminoacyl synthetase (the enzyme that attaches the amino acid to the tRNA). Each tRNA has its own aminoacyl synthetase which specifically recognizes it and attaches the correct amino acid to it.
This has the consequence that, if you load a tRNA that would normally carry one amino acid with a *different* amino acid, that second amino acid will be incorporated into the protein as if it was the first one. (This kind of mischarging of tRNAs occurs regularly in our cells and is a major source of errors in protein translation.) This fact has been known for more than half a century.
Thus: no, as far as we know, there are no chemical properties of the UUA codon that mean it has to code for leucine. The fact that it codes for leucine derives purely from the tRNAs that happen to be around; you can (and we have) replace the UUA tRNA-aminoacyl synthetase pair with a different pair that also recognizes UUA but will be charged with a different amino acid, and then that amino acid will be incorporated instead in any place where a gene contains the UUA codon. This kind of tRNA difference also occurs naturally; certain archaea use a slightly different set of tRNAs than we do and have a slightly different triplet code as a result. Closer to home, our own mitochondria also have a different triplet code; for example, two of the codons that in our nuclear DNA code for arginine instead are stop codons in mitochondria. *(Edit: this is actually a poor example, both because a. stop codons in general are not recognized by tRNAs and b. these particular stop codons are apparently quite weird in how they operate. A better example would be the reassignment of the UGA stop codon to tryptophan in mitochondria, or the reassignment of the AUA isoleucine codon to methionine/start.)*
This kind of codon refactoring is very useful in synthetic biology, because it lets you make proteins containing unnatural amino acids. However, since replacing all the amino acids in any proteins made from genes that happen to include that codon is generally pretty bad for an an organism, a necessary first step if you want it to work properly is to make an organism that doesn’t use the codons you want to replace in the rest of its genome, which we did in *E. coli* in 2019 (see [this paper in Nature](https://www.nature.com/articles/s41586-019-1192-5)).
As always with biology, things are probably more complicated than this – I did find a few papers claiming that there was some evidence for direct recognition of the amino acid by the ribosome, for example – but any such effects have to be minor given that tRNA replacement as I’ve described it above is possible.
Hope that’s helpful!
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