I don’t just go around rocking a lab-coat cape. I work on studying PROTEINS’ shape! Amino acids make proteins “charm”-ing 😍 & put the STRUCTURE in structural biology! (along with their nucleotide friends)). But what do we mean by structure? When we talk about “structure,” we’re usually referring to the overall 3D structure, but PROTEINS HAVE LAYERS OF STRUCTURE underneath the final product we “see” – primary, secondary, tertiary, and sometimes even quaternary – add it all up to get something extraordinary.
When asked what structural biology is, we often say things like: it’s a branch of science that involves looking at the molecular structure of biological “macromolecules” & working out how that STRUCTURE relates to their FUNCTION. Usually the “macromolecules” we’re looking at are proteins or protein/nucleic acid (RNA &/or DNA) complexes. They’re macromolecules because they’re made up of lots (macro) of connected smaller molecule “letters”. In proteins, the letters are amino acids & they’re not connected just willy-nilly.
There are 20 (common) amino acid “letters” & we call the order they’re connected in (amino acid sequence) the PRIMARY STRUCTURE & it’s specified by the DNA in the that protein’s gene (DNA (and its messenger RNA copy)) with 3 DNA/RNA letters (nucleotides) “spelling” one protein letter (amino acid). more here:http://bit.ly/2TBFLsU
Amino acids all have the same generic part 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 and kicks off a water. 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!
Protein’s aren’t just a long chain – they fold up – because each amino acid also has a unique part (side chain). You can picture it kinda like a charm bracelet, where the chain links are the generic peptide backbone and the side chain is like the charm that sticks off. The side chains have different properties (e.g. some are big & bulky, others small & flexible, some are + charged, others – charged, some love water, some hate water, etc.) (for lots more, check out#20DaysOfAminoAcids).
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). So even through a “sequence” might not seem like any sort of “structure,” the amino acid sequence is key to the final structure – you might even say it has *primary* importance…
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.
Turns out, there are a couple common motifs by which parts of proteins can maximize favorable interactions – alpha helixes and beta pleated strands – and the the ribbon structure representation of them was developed by Jane Richardson, who I’ve had the honor of meeting several times and you can learn more about her here:http://bit.ly/2Qcqmhn
So backbone -backbone interactions give you that secondary structure, but side chains don’t want to miss out! Side 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)
All these interactions above the primary level are reversible because they’re individually weak but collectively strong charge-based attractions. and since they’re weak attractions, the protein can change shape (this dynamic-ness allows them to do things like clamp down around substrates, help those substrates react, then open up so they can fall out. We call the shape a protein takes at any one point a CONFORMATION. And the shape-shifting’s a CONFORMATIONAL CHANGE
The charms can change their interactions, but NOT their ordering, because the peptide bond “chain links” are STRONG COVALENT BONDS. If we want to change the ordering (primary structure) we have to change the gene, which we can do through site-directed mutagenesis 👉 http://bit.ly/2Uz3Jtw
We can “see” what proteins look like using techniques like x-ray crystallography – where you get a bunch of the protein to all lock together in the same conformation. Then you beam x-rays at them, see where the beamed beams end up and work backwards to find out where they came from. more on how that works here 👉http://bit.ly/2qlzlRS
This post is part of my weekly “broadcasts from the bench” for The International Union of Biochemistry and Molecular Biology (@theIUBMB). If you want to learn more about atoms themselves (the level “below” the primary structure) check out my post from last week. http://bit.ly/2wvkWWv And be sure to follow the IUBMB if you’re interested in biochemistry! They’re a really great international organization for biochemistry and I still can’t believe they chose me to be a student ambassador 🙂