I know this sounds corny, but I’m so incredibly humbled & grateful for outpouring of volunteers translating my infographics on #COVID19 testing. I never in my wildest dreams would’ve thought I could have a global impact & I feel such a sense of purpose in these hard times. I continue to be hard at work formatting and uploading all of the translations but it takes some time so sorry for the delays and thank you for your patience. You all are awesome! Given their time-sensitive nature, I’m going to prioritize them these next couple of days and just repost past posts to tide you over. And, since translation is on my mind, naturally I figured I should review my favorite type of translation – the biochemical process in which protein is made! So, enjoy (hopefully from home so we can protect the essential workers and prevent our health care systems from getting overwhelmed!)
and if you want to find those Covid-19 infographics and more information, I set up a specific page on my blog where you can find them all: https://bit.ly/covid19bbresources
I’m especially excited about the Slovenian version I added today, because it was translated by my labmate Katie Meze who inspired this whole translating thing! Thank you!
Going to the ribosome chapel and we’re gonna make a protein! And you’re invited! I like to talk about genes (written in DNA) as the “recipes” for “baking” proteins (written in amino acids). But when it comes to the details of that “baking” process, which is called TRANSLATION, I find it easier to explain as a wedding.
[note: This was originally posted as one of my first posts as student ambassador for the @IUBMB (the International Union for Biochemistry and Molecular Biology) and I was (and remain) incredibly grateful to them for helping give me a platform to reach biochemists around the world – especially important as the world goes through the covid-19 pandemic together – thank you!]
Through my (still-excited-about) role as student ambassador for the @IUBMB, I’ve showed you cool stuff about a couple types of molecular building block “alphabets” – nucleotides, which join together to make nucleic acids (DNA & RNA) & amino acids, which join together to make proteins. (links at bottom) And I told you that the DNA had the “instructions” for making the protein, a process that’s carried out by complexes called ribosomes. But how does the ribosome read the instructions if they’re written in a different language? You need to TRANSLATE!
TRANSLATION is the process of putting together proteins one piece at a time. The pieces are called AMINO ACIDS. There are 20 (common) ones and they link together through peptide bond “marriages” carried out in a ribosomal “chapel.” The marriage order is specified by the messenger RNA (mRNA) which is a “multi-multi-use” but “disposable” RNA copy of the permanent DNA gene.
RNA (ribonucleic acid) & DNA (deoxyribonucleic acid) are both written in the “nucleic acid” language (did the name give it away?), where the letters are nucleotides (sugar+phosphate+nucleobase(1 of 5 unique options)). RNA & DNA are really similar (they just have a different sugar and 1 of the nucleobases is slightly different). Since they’re both in the same “language” we call the DNA->RNA copying process TRANSCRIPTION. But when you go from RNA to protein you’re changing into the protein language which has amino acid letters, so we call this process TRANSLATION, and it reminds me of a (very polygamous) marriage.
We’ll go into it in more detail (& I’ve provided links to even more) but these are the “main events” in planning a protein wedding (TRANSLATION):
- you’ve gotta put down a deposit -> amino acid ACTIVATION (add AMP to amino acid) +$
- you need to find & get in the right limo -> tRNA charging (add amino acid to tRNA “carrier”) -$
- you need to get the right loaded limo to the chapel at the right time -> tRNA binding (bind tRNA to mRNA “instructions” in ribosome “chapel”
- you need to tie the knot -> peptide bond formation (transfer growing chain to newcomer – you’re marrying someone who’s already married a bunch of people)
- you need to clear the altar for the next bride or groom -> elongation factors spend GTP money to change shape and “push” the mRNA/tRNA along & kick the tRNA off$
- you may have to pay security to kick out some uninvited guests -> hydrolytic editing $
Let’s get this wedding party started, shall we? Initiation factors say “Yes, we shall!” The wedding party gets started when the ribosomal chapel assembles itself (with the help of initiation factor “construction workers” around the first bride (which is always a methionine (Met) because its codon also serves as a start signal. more on translational initiation: http://bit.ly/2KNe00D
Amino acids are taken to the chapel by transfer RNAs (tRNAs) which serve as “limos.” Each tRNA will only accept one type of amino acid (but there are lots of identical copies of all of these things, so there’s hopefully plenty to go around). Each amino acid has at least one tRNA just for itself and it’s important that the right amino acids get in the right limo because the ribosomal “priest” won’t be able to tell what amino acid’s in the limo, just what limo it is (by “reading” the limo’s “license plate” – a 3 RNA letter word called an anticodon that complements a codon on the mRNA. more on this genetic code: http://bit.ly/2TBFLsU
It’s really important that there’s no identity theft allowed! Your cells have to pay for this added layer of security in the form of energy money. In AMINO ACID ACTIVATION, an AMP molecule is added onto the amino acid from ATP. Then, in the tRNA CHARGING step, the amino acid binds to the matching tRNA (the one whose anticodon “license plate” matches the codon “reserved parking for…” sign in the mRNA. The AMP is released in the process, leaving you with aminoacylated tRNA (aa-tRNA). more: http://bit.ly/2GhbFps
We call it “charging” because phosphate bonds are “high energy” – they don’t like being held in one spot – especially next to other phosphate groups, which repel them – literally – because of the negative charge-negative charge situation. ATP’s happy to give up phosphate(s) because it’s like releasing a spring. more on this here: http://bit.ly/2WiPOpg
So, now you’ve “paid” your deposit, it’s time to start heading to the chapel. But you’ll want to take a “security guard” to make sure you don’t go to the wrong place. ELONGATION FACTORS (EF-G in bacteria and EF-1 in humans) travel with the aa-tRNA and don’t leave until they make sure that the codon and anticodon match (note that it’s the anticodon that matters here, not the actual amino acid, which is why that precaution during the charging step is important) – you don’t want to drop off imposters!
Once the EF sees all’s good, it “pays for the aa-tRNA’s parking” by hydrolyzing (using water to split) GTP into GDP (same concept as usage of ATP for energy, just a different nucleobase), & this time the energy’s being used for shape-shifting. When it’s bound to GTP the EF has one shape, but when it’s bound to GDP it has another shape. So, after splitting the GTP, it “splits” -> falls off
The EF drops off the incoming tRNA in the ribosome’s “A” spot (1 of 3 parking spots that fit in the ribosome at a time). The ribosome then carries out its priestly functions, uniting the new amino acid with the growing peptide chain through a PEPTIDE BOND union. The growing strand gets transferred to the new tRNA, so you have an awkward transition stage where the peptide’s still mostly in the P spot but it’s attached to a tRNA that’s in the A spot. Another elongation factor, (EF-Tu in bacteria or EF-2 in humans) comes in and moves things along, spending GTP to push the old limo (still attached to its mRNA parking spot) into the E spot (where it falls off), the limo with the growing chain into the P spot, and bringing a new codon into the A spot for the next amino acid to be added.
Something special happens when a “stop codon” shows up there. This signals the end of the chain. Instead of a tRNA binding it, a protein TERMINATION FACTOR binds and cleaves the chain off. more on translational termination: http://bit.ly/2IFmmEZ
The superpolygamous protein can then make itself comfortable by folding into the optimal conformation so that the amino acids that like each other are kept together, ones that hate each other are kept apart, etc. like we talked about here: http://bit.ly/2KBFRiS
more on proteins: http://bit.ly/2KBFRiS
more on nucleic acids: http://bit.ly/2FqasfN
more on topics mentioned (& others) #365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0