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Tertiary structure of proteins
How side chain interactions can impact the tertiary structure of proteins.
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Why do the polypeptide chains in specific proteins always form the same structure, rather than (randomly and opportunistically) forming different bonds and structures each time they form within the aqueous cell environment?(18 votes)
This is a very insightful question - if you were to chemically synthesize a protein and throw it into solution it would most likely not fold properly.
The non-teleological reason why proteins take on one (or only a few) forms, is based on the energetics of how they fold. Most proteins have one highly stable tertiary structure, which is often organized around a core region of hydrophobic residues. However, if you denature proteins (e.g. by heating them up) and then let them cool they usually fail to reform into the 'correct' structure - instead they stick to each other. An everyday example of this happens when an egg is boiled - the white {mostly protein} goes from a transparent goo to an opaque white solid.
So why doesn't this happen in cells as new proteins are made?
A major factor is that the protein begins folding into secondary structure elements as it is made. These then can assemble into tertiary structural elements called domains (more or less independent substructures). This means that the new protein only needs to 'figure out' the right way to fold a small amount of of the total protein at once - this is clearly much simpler (more constrained) than what happens with a denatured protein.
Another part of the answer is that proteins called chaperonins keep proteins from sticking together randomly and help the new protein find (one of) its most stable (lowest energy) form(s) — this is particularly important for proteins that must be bound to other proteins to make a stable structure. Note, that this is an active area of research ...
For more information this wikipedia article seems quite good: https://en.wikipedia.org/wiki/Protein_folding.
Also, some proteins can take on more than one structure (though this is not random) and most have regions that are unstructured.
An important example of proteins that can take on radically different forms are prions (https://en.wikipedia.org/wiki/Prion).(41 votes)
At3:05
Why are hydrocarbons hydrophoc if Carbon is much more eletronegative than Hydrogen?
Wouldn't it nab H's electrones and then gain a partial negative chrage transforming it in a polar molecule?(4 votes)
Carbon is not significantly more electronegative than hydrogen. They have roughly the same electronegativities, which is why a carbon-hydrogen bond is nonpolar.
Also important to note, the polarity of a molecule depends on its asymmetry, not the polarity of the bonds. Hydrocarbons tend to be nonpolar because they tend to be symmetrical molecules, which is why they are hydrophobic.
I hope I helped!(29 votes)
I have textbook which suggests that the ionic bonds which form to give a protein its tertiary structure form between 'any carboxyl and amine groups that are not involved in forming peptide bonds'. They make no mention at all of side chains.
I can't really see how this could be correct - how can ionic bonds form between groups with stable electron arrangements and no charge?
So my question is: do the ionic bonds that make up a protein's tertiary structure only form between charged side chains (as this video seems to suggest), or is there an element of truth also to what is said in my textbook? And, if my textbook is also right, how can ionic bonds form between a carboxyl group and an amine group?
I'm pretty confused, and would be very grateful for any help. Thank you.(5 votes)
What your textbook said is correct but by using broader terms.
So, for ionic bond, partially negative and partially positive charges are required.
Any carboxyl or amine groups that are not involved in forming peptide bonds means all side chains. Any group (no matter if carboxyl or H atom) if not involved in forming peptide bond is side group which can react with other side chains.
For instance, aspartic acid is charged amino acid, and that charged part which interacts information of ionic bond is nothing else but carboxy group not involved in forming peptide bond!
Does it make sense now? :)(5 votes)
- How do you know which elements bond which other elements in a covalent or ionic bond? Is there dehydration synthesis?(2 votes)
- A covalent bond is between nonmetals.
An ionic bond is between metals and nonmetals.
Dehydration synthesis takes place information on the peptide bond.
Once you come close to the molecular level you see which molecules are bonded and presumably know, OH and H were eliminated (meaning H20 molecule).(4 votes)
In my biology class I was told that in a beta pleated sheet the R groups point up or down if you think about it in 3D. How would the R groups then bond to each other if they are not oriented towards each other? I am having difficulty visualizing this.(2 votes)
If the sheet is antiparallel they point in the same direction and away if parallel.
If you combine both types you can form bonds.
One parallel pleated sheet can not bond with itself though - only in combination with other sheets.(5 votes)
- Do side chains ever bond to other parts of the backbone that aren't part of the same amino acid?(3 votes)
- Why humans cant able to make essential amino acids(2 votes)
- Because we lack enzymes which are responsible for converting metabolic precursors into those amino acids.
During evolution, mutations led to a loss of enzymes. Why? Because it turned out to be a heavily energetic process and it was more beneficial for us to intake amino acids through diet than to produce them by our bodies.(2 votes)
- I don't understand how Helix structure is different from parallel and anti-parallel. Only thing I understand is that Helix structure is "h-bond between layers". But aren't all these structures, i.e. parallel and anti-parallel also "h-bond between layers"?(2 votes)
- Do you know the mening of parallel in mathematics? Two lines which are aligned.
Antiparallel would be parallel - but the second strand is going in reverse direction.
DNA id double helix with antiparallel straucture. So certain moelcuel can be both.
Helix is not synonym to parallel.(2 votes)
- Is the long winding structure on the right a single protein, or multiple proteins stuck together?(2 votes)
- Talking about the secondary structure, is the backbone forming only hydrogen bonds, or can it interact also through other kinds of bonds?(2 votes)
3:05Video transcript
- [Voiceover] In the video on protein structure, we talked about the different orders of structure, starting with primary structure, and this is all a bit of a review right now. Primary structure is just a sequence of the amino acids. But then from there we can start thinking about how does it get shaped by thinking about the secondary structure. And secondary structure is all about interactions of the actual backbone, and we went into some depth in the overview video where we talked about some of the more typical secondary structures. We talked about the parallel beta-pleated sheets, and over here I have two backbones. They're oriented in the same direction. Nitrogen, alpha carbon, carbonyl carbon. And I just drew the side chains as these generic R groups. And what we saw is you can have hydrogen bonding between these backbones, and that was a parallel beta-pleated sheet. Or if they're oriented the other way, this one's going nitrogen, alpha carbon, carbonyl carbon. This one's going carbonyl carbon, alpha carbon, nitrogen. Well now you have an anti-parallel beta-pleated sheet and once again, this is interaction of the backbone. Or you could have an alpha helix like this where you have hydrogen bonds between the different layers of your actual helix. And then we can get to tertiary structure, and tertiary structure is where we finally talk about interactions of the side chains, where we start to think about, well, what are these R groups and how would these R groups actually affect the entire shape of the protein? And to help us think about that a little bit, I've drawn a few visuals down here. And so what you could imagine, you could imagine this orangish-brown string curve that I've drawn here, let's just assume for the sake of visualizing that that's our polypeptide backbone. And just as a bit of review, you could think about your first order, your primary structure, which would be about, okay, I have that amino acid, then I have this amino acid and then I have that amino acid. So that sequence, the sequence is your primary structure. Then you could have interactions between the backbone, and so that could be maybe this is a, this right over here, this is an anti-parallel beta-pleated sheet right over here where you have hydrogen bonds. I'm trying to draw a dotted line, but it's really small. Where you have the hydrogen bonds right over here between these two backbones. I haven't drawn the side chains here. You could have an alpha helix here. Once again, you have hydrogen bonds between the layers of the helix. But now let's talk about tertiary structure. And tertiary structure's about the side chains. So one example of tertiary structure, here I've drawn a bunch of side chains. This is from valine, I haven't drawn the backbone. The backbone's up here. And obviously, none of this is drawn quite to scale. But the valine side chain, its R group is pure hydrocarbon, which is hydrophobic. And so one common interaction you might see from side chains is hydrophobic side chains are not gonna want to be on the outside of a protein molecule that's inside of an aqueous solution, that's being exposed to water. So this might wanna clump into the center, and so that might affect how that chain, how the polypeptide chain is bent or how the whole protein is shaped. So these, for example, these might be hydrophobic. These would be hydrophobic here and kind of they're clumping away from the water. And I'm drawing everything in two dimensions, but obviously proteins exist in three dimensions, which makes their shape so interesting and oftentimes hard to fully process. You could have something like serine which has a hydroxyl group on its side chain. And a hydroxyl group, one, since it's polar, we know oxygen is a lot more electronegative than hydrogen, so the oxygen's going to have a partially negative charge. This hydrogen's going to have a partially positive charge. So that's going to allow this side chain to be more hydrophilic, so it might sit on the outside of a protein in contact with an aqueous solution. Or it might even allow it to form hydrogen bonds with other side chains. So let's say that you had the side chains go like this. And once again, I'm not drawing it anywhere near to scale. I'm exaggerating the size of these side chains. But maybe you have another side chain that, I'll just draw it like this. You have another side chain that at some point, you know, it's got a bunch of stuff. And then it has a, I'll just draw dots here. It has a bunch of stuff, but then it has an oxygen bound to a hydrogen. Bond to a hydrogen. Well, maybe you have some hydrogen bonding going on like that, so that would also keep this structure in place. You could have situations where you have ionic side chains, side chains that have charge. So maybe this side chain right over here, maybe it has a positive charge. And our polypeptide backbone, let me loop it back this way just like that. You could have another side chain. You could have another side chain that has a net negative charge, and so these are going to be attracted to each other and you're going to have an ionic bond. You can even have covalent bonds between side chains. This right over here, this is a typical covalent bond that might be formed between two cysteine side chains, both of which contain sulfur. When they're left to their own devices, each of these sulfurs, let me just, so it's cysteine, this is the nitrogen, this is the alpha carbon, this is the carbonyl carbon. So I'm trying to draw the section of it that is cysteine. So when it's not in one of these disulfide linkages, this sulfur right over here would have a covalent bond with a hydrogen. But under the right circumstances, it can form a covalent bond with another sulfur. And in this case, it's another cysteine side chain right over here, and this thing over here, this is a disulfide bond or disulfide linkage, sometimes called. And so you can imagine if let's say this was a cysteine molecule, this part of the backbone, this is cysteine, this is cysteine, that their two side chains can form this disulfide linkage, and so that would kind of provide kind of almost a clip to clip those two parts of, or that part of this entire polypeptide together. So hopefully this gives you an appreciation for all of the interactions that might occur to give a protein a structure. And then last but not least, of course, you have the quaternary structure, which is how do you fit together multiple polypeptide chains? And all of these, this whole series of videos, is just to give you an appreciation for, even if you know the sequence, the different shapes and the different interactions that a protein can actually have, and that's what gives proteins their complexity, their beauty, their ability to provide all of these functions to catalyze reactions as enzymes, to be signals as hormones, to provide structural integrity, to help transport oxygen, as in the case of something like hemoglobin. And it's a huge area of research. Even if you know the sequence, what is the shape of that protein, and based on that shape, how can we use that to think about how to manipulate that protein in different ways or who knows? So it's a fascinating area of research.