“Cognate” (in the context of biology) basically means “correct” – when you see it, think “recognize” because molecules are able to “recognize” their “correct” (cognate) binding partners based on them providing favorable binding interactions. “Non-cognate” (wrong) molecules won’t be able to bind stably, so interactions will typically only be transient. This is how, for example, cellular receptors are able to specifically respond to some signaling molecules but ignore others. 

YouTube: https://youtu.be/fNRtUxTgtk8 

But sometimes, molecules can be “tricked” into binding and even using wrong molecules because they’re near-cognate. They’re similar, but not exact. And this can cause problems in the context of translation, where ribosomes (protein making machinery) travel along a messenger RNA (mRNA) transcript and piece together the amino acids brought to it by transfer RNAs (tRNAs) following the mRNA’s recipe, which is spelled out in three-RNA-letter “words” called codons. 

In order to make the proteins by the book, the ribosomes need to be able to discriminate between cognate incoming tRNAs (the correct ones, those that complement the mRNA codon in the A site and hold onto the corresponding amino acid) and near and non-cognate ones (which don’t quite match and have the “wrong” amino acid attached). 

Thankfully there are multiple safety checks involved in this “decoding” step, allowing ribosomes to make few typos (mid-incorporations of amino acids). These checks include enhanced stability of cognate tRNA-mRNA and tRNA-ribosomal RNA interactions leading to stabilizing shape-shifts (conformational changes) in the ribosome. Additionally, the tRNA is brought by a helper molecule called an elongation factor and if it senses that the fit is good, it hydrolyses (splits) GTP providing an energy boost that helps promote the amino acid-adding process. If things are awry, the interaction hopefully won’t be stable enough for all that to happen before the tRNA/elongation factor complex just falls off. 

Something that can be confusing is that often only the first 2 positions of the anticodon have to match the codon. The third position is called the “wobble position” and there’s more flexibility here. This allows the same tRNA to recognize multiple codons  that all spell the same amino acid, so you don’t have to have a separate tRNA for each codon. You just need to make sure that each tRNA only recognizes codons that correspond to the amino acid it has attached to it. For this reason, if you look at a codon table, which shows you which codons correspond to which amino acids, you’ll see that things are kind of clustered by amino acid because for any given amino acid the first 2 positions are often the same but the 3rd can vary. But this isn’t always the case. 

Because of that wobbly exception, anticodons can still be cognate (but aren’t necessarily) if they have a mismatch at the 3rd position. But, if they have a mismatch at the first and/or second position they’ll be wrong. Just one mismatch and we say it’s near-cognate: 2 and we call it non-cognate. 

One other thing that can be confusing is you need to not mix up “wobble position” and “wobble pairing.” Although wobble pairing is often found at the wobble position, these are different things. “Wobble pairing” typically refers to a weird, “non-canonical” interaction between G and U. It still involves hydrogen bonding, but it’s shifted (see the pics). 

There are also safety check steps that happen before the tRNA even reaches the ribosome. Because you need to make sure that only the right (you could say cognate) amino acids get added to each tRNA. This checking is done by the enzymes (reaction helpers) that do that amino acid adding (aminoacyl-tRNA synthetases). More on that here: blog: https://bit.ly/aminoacylation  ; YouTube: https://youtu.be/CVXlHsFH_yo   

And much more about translation here:blog form: https://bit.ly/proteintranslationwedding  ; https://youtu.be/77aVShrXq-Q

further reading:

• Blanchet, S., Cornu, D., Hatin, I., Grosjean, H., Bertin, P., & Namy, O. (2018). Deciphering the reading of the genetic code by near-cognate tRNA. Proceedings of the National Academy of Sciences of the United States of America, 115(12), 3018–3023. https://doi.org/10.1073/pnas.1715578115 
• Joshi, K., Cao, L., & Farabaugh, P. J. (2019). The problem of genetic code misreading during protein synthesis. Yeast (Chichester, England), 36(1), 35–42. https://doi.org/10.1002/yea.3374 
• Marcus Fislage and others, Cryo-EM shows stages of initial codon selection on the ribosome by aa-tRNA in ternary complex with GTP and the GTPase-deficient EF-TuH84A, Nucleic Acids Research, Volume 46, Issue 11, 20 June 2018, Pages 5861–5874, https://doi.org/10.1093/nar/gky346
• Ogle, J. D., Murphy, F. V., Tarry, M., Ramakrishnan, V. (2002). Selection Of Trna By the Ribosome Requires A Transition From An Open To A Closed Form. Cell, 5(111), 721-732. https://doi.org/10.1016/s0092-8674(02)01086-3 
• Rudorf S, Lipowsky R (2015) Protein Synthesis in E. coli: Dependence of Codon-Specific Elongation on tRNA Concentration and Codon Usage. PLOS ONE 10(8): e0134994. https://doi.org/10.1371/journal.pone.0134994

more about all sorts of things:  #365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0    or search blog: https://thebumblingbiochemist.com