The purpose of translating my Covid-19 test infographics into additional languages it to reach people around the world and help provide a little clarity in this time of immense uncertainty (thanks again to all my helpers!) The purpose of translating in the biochemical sense is to make proteins by following genetic instructions! But what exactly is a protein? As I continue to work on adding translations for you, here is an amino acid (protein letter) to peptide (linked amino acids) to protein (folded-up peptide) review!
For all those translations (and more covid-19 resources, check out https://bit.ly/covid19bbresources
This post was posted in its original form as the kick-off to my December biochemical “advent calendar”: #20DaysOfAminoAcids, and you can find all those posts, and other amino acid resources here: https://bit.ly/aminoacidsposts
Those posts include individual profiles of the 20 (common) amino acids (and a couple of uncommon ones). They all have the same generic part for linking up, which has 2 reactive sides: a carboxyl group (C=O)-OH) and an amino group (NH₃) – the genericness lets any of them link to any other of them through strong covalent PEPTIDE BONDS in which the amino group of one latches onto the carboxyl group of another. Link up a few (oligo) to get an oligopeptide or a lot (poly) to get a polypeptide. A protein’s just a polypeptide with a plan!
That “plan” depends on the unique parts of the amino acids – the “side chains” (aka R groups) that stick off like charms on a charm bracelet and can interact with each other and with other molecules – some are small & flexible, others big and bulky, some water-loving (hydrophilic), some water-avoiding (hydrophobic). Some +-charged, some —charged, some neutral. And they keep these properties when they link up – so they help make the proteins they’re part of unique too.
These properties influence how the proteins fold up (e.g. they hide the water-haters (hydrophobic residues) in the center, put + by – etc.) and how they fold up influences how they work. (e.g. maybe they fold so that they leave a nice pocket for binding something else, or they fold so that they bring together charges to form an “active site” that can do things like cut DNA).
There’s a lot you can gain from learning about each of the amino acids in isolation, but there are some properties that only really make a mark when you join them together – link them up through peptide bonds to form long chains that fold up into functional proteins. So today, before diving in to the alphabet, I wanted to give you an overview of the bigger picture – what amino acids are and why they matter. What happens when they join together to form peptide bonds and the long chains of amino acids we call proteins?
Proteins are the main “workhorses” in your cells – they help with everything from maintaining structure (no one wants crushed cells!) to breaking down food for energy, to linking up different types building block molecules into chains (polymerization).Speaking of which, proteins are themselves polymers – of building blocks called amino acids. Proteins are made (with the help of other proteins (and RNA!)) by linking up individual amino acid letters based on instructions coded for in genes, written in DNA.
The basic story goes like this: cell decides it wants to make a protein -> RNA polymerase makes a messenger RNA (mRNA) copy of the protein’s DNA instructions (transcription) -> edits that copy to remove regulatory info (splicing) and give it a cap & tail to tell the cell it’s legit & help with downstream stuff -> hands this mature mRNA over to a protein/RNA complex called the ribosome, which reads it in 3-RNA-letter words called “codons” that spell 1 amino acid letter (e.g. if it sees the sequence GCCUCU it’ll link together the amino acids Alanine & Serine, which are spelled “GCC” & “UCU” respectively and brought to the ribosome by transfer RNA (tRNA) that has a matching anticodon).
Proteins can range in size from tens to thousands of amino acids. The longest – titin – is a titanic > 34,000 amino acids long! Its huge size & flexibility helps it to anchor the moving parts of your muscles so they can expand and contract but always come back! Most proteins aren’t that long though. The average is ~300 with bacteria having slightly shorter (average of ~250) than eukaryotes (a class that encompasses most things other than bacteria), which have an average ~350.
No matter their length, each protein has a distinct combo of amino acid letters. And those letters keep their unique properties when they link up to form proteins, so different proteins (with their different “spellings”) have different properties and are well-suited for different tasks. One of the main ways amino acid uniqueness affects the protein is by influencing how the protein folds up into a “final” 3D structure (I put final in quotations because even the “finished products” are dynamic – flexible parts can shape-shift to allow the protein to carry out various tasks). And that 3D structure makes that protein well-prepared for the tasks it’s tasked with.
We can talk about “levels” of protein structure – PRIMARY STRUCTURE refers to the protein’s sequence – it’s amino acid spelling – even through a “sequence” might not seem like any sort of “structure,” the amino acid sequence is key to the final structure because of the unique properties we’ll dive into this month.
But the backbone still matters -> in addition to the strong peptide bonds between next-door neighbors in the chain, the backbones can interact with other parts of the backbone through weaker, non-covalent bonds. These interactions between the backbone (but still in the same polypeptide chain) leads to SECONDARY STRUCTURE (things like alpha helices & beta strands). But side chains don’t want to miss out – chains can also interact with other side chains and other backbone parts. When they do so within the same polypeptide chain, we call it TERTIARY STRUCTURE – between chains is QUATERNARY STRUCTURE – this can be between copies of the same chain or completely different chains. (I can never remember if there’s a 3rd R in quaternary seems like there should be but there’s not)
Protein structures may be dynamic, but they’re not too loosey-goosey – it wouldn’t be very helpful to have cells filled with spaghetti! Instead, their movement is restricted by some special properties of the bond linking them together – the peptide bond. Before we think big, let’s think really really small.
Amino acids, like all matter for that matter, are made up of atoms which are the basic units of elements (things like carbon (C), hydrogen (H), nitrogen (N), & oxygen (O)) – see the Periodic Table for a full menu. Different elements have different numbers of tinier things called protons. These + charged subatomic particles hang out in a central core called the nucleus (along with neutral neutrons) and their positive pull helps reign in a cloud of negatively-charged electrons that whizzes around them (kinda like super hyper dogs on leashes).
The outermost electrons are called valence electrons. They’re furthest from the nucleus’ pull, have the most energy, and can interact with electrons from other atoms. Since opposite charges attract, protons have electron pulling power, but so do other + charged things in other molecules.
So electrons can get attracted to other molecules and drag the rest of their molecule along with them to investigate. Like it enough and the 2 molecules might end up sharing a pair of electrons to form a covalent bond. They can even share 2 pairs to form a double bond or 3 for a triple. Since both atoms are invested in these bonds, they’re strong, especially when they have multiple electrons in the game (like in a double bond)
You can think of a covalent bond as a kind of reign – the more electronegative, the tighter the reign and add a second like you have in a double bond and that’s some strong reigning-in potential! So double bonds are stronger than single bonds and they’re shorter.
Another consequence of double bonding is that it prevents twisting. Whereas a single bond’s rotatable, a double bond’s kind like if you stand across from someone and try to shake both hands while twisting around. Molecules can’t do that sort of contortionism. So, as a result, movement around a double bond is restricted
Another thing about electron-sharing is that. when atoms share electrons, they don’t always do so fairly. One of them may hog the shared electrons and we say the hogger is ELECTRONEGATIVE.
Oxygen’s one of those really hoggy ones. And in biochemistry it shows up a lot. And a lot of the time it shows up double-bonded to a carbon (C). We call such a -(C=O)- a carbonyl. You’ll find these in a lot of places in biochemicals – it’s 1 of most important “functional groups” because the O pulling e- density away from the C makes the C more reactive because it’s positively desperate for some electron-rich friends (we call such electron-seeking things electrophiles and you can learn more about them here – http://bit.ly/2KXq9OU )
A functional group’s just a commonly-found atomic combo that has certain properties that it keeps regardless of what it’s stuck onto. Like how you could tape a spoon to anything and still (albeit potentially with great difficulty) scoop ice cream with it, whereas you could tape a fork to it and not have luck – but the fork would still have its fork-useful-ness. More here: http://bit.ly/2IXlz0i
So, going back to this “biochemical spoon of sorts.” O had 6 electrons “of its own” going into the bond, so even with those 2 electrons of is going towards the double bond, it still has 2 “lone pairs” of electrons that attract hydrogens that are attached to electronegative things like N or O and are thus (δ+). When an electronegative atom with a lone pair (like the O in a carbonyl) is attracted to an H attached to an electronegative thing, you get something called a hydrogen bond (H-bond). It’s not a strong bond like the covalent bond (no actual electron sharing, just attractions) but they can add up. There’s structural strength in numbers – and there are lots H-bonds in proteins!
But that O needs its scaffold and that’s where carbon (C) comes in. It has 4 electrons “of its own” to share. It can give 1 to each of 4 other atoms to form 4 single bonds, or double or triple up to connect more strongly to fewer atoms. When it forms a double bond, like in a carbonyl, that takes 2 electrons, so it still has 2 left.
when C=O is attached to an alkyl group “R” (H or C attached to Rest of molecule) on 1 side it’s called an ACYL & still has free side. And depending on what that free side’s attached to, we give it different names.
If it’s attached to OH we call it a CARBOXYL. Since when an H is attached to a hoggy O it can come and go, a carboxyl can exist in 2 forms: if O’s bound to H it’s a CARBOXYLIC ACID. When that acid acts as an acid (donates an H⁺) we call the O deprotonated and call it a CARBOXYLATE (which is the conjugate base of the carboxylic acid – more on acids and bases: http://bit.ly/2Zj3mFe
Without the + of the H⁺ , the carboxylate is negatively charged, so we call it an ANION (as opposed to positively-charged things which we call cations).
When the (C=O) is attached to nitrogen (N) we call it an AMIDE. N is similar to O in a lot of ways – both are electronegative and have lone pair(s) of electrons – but O has 2 lone pairs whereas N only has 1 (and 1 more electron free for bonding). So N can also form H bonds when that lone pair’s not in use. And sometimes an N uses its lone pair to snatch up a proton like the ones acids pass out.
You’ll find both of these – carboxyl & amide – when you start linking up amino acids. Amino acids revolve (literally & figuratively) around a central carbon (Cα). C can form up to 4 bonds & Cα makes use of all of em. On 1 side it bonds to an *amino* (nitrogen/hydrogen) group 👉 other side a carboxylic *acid* group (-COOH) 👉 AMINO ACID!
The other 2 bonds? 1’s to H & other’s to an “R GROUP” (aka SIDE CHAIN) 👉 part that makes each of the 20 aa unique.
Amino acids join carbonyl (C=O) group of one to amino group of other ⏩ “CONDENSE” to form PEPTIDE BOND (aka amide bond) – individual amino acids have carboxyl groups and when they link up they swap that carboxyl for an amide. On net this requires the loss of an OH (from the carboxylic acid) & an H (from the amine group) so, 2 H & 1 O – H2O – water. So this is also known as a dehydration reaction – but when your cells do it they don’t directly lose water cuz they do it stepwise.
PEPTIDE BONDS are special because they’re resonance-stabilized. Chemicals want stability & a great source of stability is RESONANCE (delocalized e⁻ sharing). In order for electrons to be shared through resonance they have to have their electron clouds synced up just right – you need them to all be on the same plane (planar). Think of a hose – if you want water to flow through the hose you can’t have the hose pinched – atoms have to stay “flat” to share. So they trade charge stabilization for some restriction of movement.
ELECTRONEGATIVE (e⁻ hogging) O of carbonyl pulls so hard it drags e⁻ density from N (which has a lone pair) even though there’s a C between them. This e⁻ delocalization is very stabilizing BUT it can only occur if atoms are lined up in the same “plane” – so the peptide bond is PLANAR – no rotation is allowed
Each time you join 2 amino acids, you lose the carboxyl (but keep the carbonyl!), gain an amide, & form one of those planes. And keep combining amino acids like this & you get a “chain of planes” connected at Cα “nodes.” Because of that whole resonance stabilization needing stiffness, there’s NO rotation about C-N bond. BUT you DO have rotation around other backbone bonds. These ⟳ are between 2 planes so we call them DIHEDRAL ANGLES (aka TORSION ANGLES). And, like a Geek sorority, they have Greek names.
- phi Φ : ⟳ about N-Cα
- psi Ψ : ⟳ about Cα-C
tips for remembering 👉 psi sounds like it could start w/C & looks kinda like a sideways C on a stick 🤷♀️
These ⟳ are possible because you can rotate “freely” around single bonds, BUT they aren’t really “free” because of STERIC HINDRANCE – basically 2 atoms can’t be in same place – the bigger the side chain, the less the flexibility
Actual angles bonds take are usually less “random” because the backbone’s perfectly placed H-bonding groups can interact to form “secondary structure” (like helices & strands) when they take on characteristic angles. In fact, you can look at something called a Ramachandran plot which shows the angles taken by atoms in a molecule. When we’re solving a crystal structure we often check that the angles are geometrically solid & one of the things you’ll see in the “report card” for a structure is “Ramachandran outliers” If people are interested, maybe I’ll do a post on these plots…
a couple other cool things:
The C-N bond has partial double bond character, so it’s shorter than normal C-N bond but longer than a C=N bond
Since the O is stealing electron density, and electrons are negative, the O becomes partly ➖ (δ-) & the things it steals from (N & H) become partly ➖ & N & its H partly ➕(δ+). High hydrogen bond (H-bond) potential! So the protein backbone is peppered with evenly-spaced H-bond donors (the N-Hs) and acceptors (the carbonyl O) – so you can get consistent H-bonding patterns perfect for things like forming the alpha helices & beta strands that give proteins their secondary structure!
I’ve focused on their protein-letter role here, but, as we’ll see as we go one by one, in addition to serving as protein letters, amino acids can serve as metabolites and (often in slightly modified forms) can function as chemical messengers. For example, tryptophan can be converted into the brain messengers (neurotransmitters) dopamine & serotonin.