Protein Folding - Video Tutorials & Practice Problems
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concept
Protein Folding
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Video transcript
So now that we've covered the Anfinsen experiment, in this video, we're gonna talk about protein folding. So protein folding actually has many different contributing factors, but it heavily relies on non covalent interactions such as the hydrophobic effect, and we'll be able to see that down below in our example of protein folding. Now, recall from our previous lesson on the Infantin experiment that the final protein confirmation ultimately depends on the primary level of protein structure and the and the final protein conformation. And so generally, the way that protein folding works is that it leads to non polar hydrophobic amino acids found on the interior of the protein, and polar hydrophobic, I'm sorry, hydrophilic polar amino acids found on the perimeter of the protein. And so we can see that down below in our example. So, on the left over here, what we have is an unfolded polypeptide chain. And the black line here represents the peptide backbone. Now, each of these red balls represents hydrophobic amino acid residues that are non polar. So we can put hydrophobic amino acid residues. And then the blue balls over here represent hydrophilic amino acid residues that are polar. And so this is our unfolded polypeptide chain. But after it undergoes protein folding, notice that the tendency is for the non polar hydrophobic amino acid residues that are in red to be tucked away into the interior because they are water fearing. And so, what initiates the clumping of all of these, hydrophobic amino acid residues is the hydrophobic effect. And so the hydrophilic polar amino acid residues are likely to be found on the perimeter of the protein because they want to interact with the aqueous water environment that's surrounding the protein. And so over here in our image on the right, essentially what we have are our 20 amino acids and the likelihood that of where we'll find these proteins after protein folding, in terms of being on the inside of the protein or on the outside of the protein. And so in this dotted box over here, we have our neutral amino acid residues, and then on the outside of the box, we have our charged amino acid residues at physiological pH. And so within our neutral amino acid residues, we've broken them up into non polar and polar amino acid groups. And so notice that we don't have our aromatic amino acid group, and that's because we've taken our aromatic amino acids, phenylalanine, tyrosine, and tryptophan, and we've distributed them amongst the non polar and the polar group. So notice that tryptophan and phenylalanine are part of the tyrosine is part of the polar group. And so we know that for our non polar amino acids, our mnemonic is GAV LIMP. And so to add in tryptophan and phenylalanine, we can say that our buddy Gavin, who's limping away on crutches away from the water, he's not limping away slowly, he's limping away way fast. And so if we add way fast, GAV limp way fast, then that'll help us remember that tryptophan and phenylalanine can be grouped as nonpolar. And the nonpolar amino acids are hydrophobic. And because they're hydrophobic, they're going to want to get away from the water, the aqueous environment that surrounds the protein. And so they're gonna be tucked into the interior of the protein just like we see over here with these red hydrophobic residues. Now to go to the opposite extreme over here, and that's because they have full charges at physiological pH. And the mnemonic to remember those is dragons eat knights riding horses. And so we've got our negatively charged and our positively charged amino acids and they are very very hydrophilic or very very water loving. And so they interact with these water molecules that are surrounding them. And so in order to, better interact with the water molecules, that are surrounding the protein, they associate themselves on the outside of the protein or on the perimeter of the protein. So these charged amino acids are the ones that are most likely to be found on the perimeter of the protein. Now, in the middle here, we have our polar amino acids, and our polar amino acids are not charged. They are neutral at physiological pH, but they are still polar, just not as polar as the charged ones. And because they are still polar, they're actually somewhat hydrophilic. So they have a little bit of, tendency to associate with water, but not as strongly as the charged ones. So for that reason, the, the polar amino acids are likely to be found either on the inside of the protein or on the outside of the protein, and pretty much an equal amount. And so they're pretty much gonna be distributed throughout our protein. And the mnemonic to remember the polar amino acids is just Santa's team crafts new quilts. And the y here for Tyrosine can be added to our mnemonic by saying, And so this here concludes our lesson on, protein folding and how the amino acids, can we can expect to find the amino acids distributed throughout our protein. And so we'll be able to get some practice with these concepts in our next, practice video. So I'll see you guys there.
2
Problem
Problem
Which of the following is the greatest contributor to spontaneous protein folding?
A
Decreased chain conformational entropy.
B
Increased chain conformational entropy.
C
Decreased entropy of the solvent due to folding.
D
Increased entropy of the solvent due to folding.
3
concept
Protein Folding
Video duration:
3m
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Video transcript
So now that we've covered the basics of protein folding, we can talk about Leventhal's paradox. And so this guy, Cyrus Leventhal, actually disproved the popular belief that protein folding was a random trial and error. Protein would have to test all of its possible confirmations before it could actually achieve its final native confirmation. And so all Levinthal did was he made a pretty simple realization. He realized that testing all the possible confirmations would simply take way too long and he knew that protein folding was super fast and was a non random process, not a random process. And what that means is that protein folding must have predictable folding pathways. And so today, scientists are able to actually predict the folding pathways for some small proteins, and this field is actually growing as we speak today. And so, like we said earlier, protein folding is super fast and really it has to do with the cooperative stepwise interactions between amino acids that makes the protein folding so fast. So they speed up the protein folding and these cooperative stepwise interactions pretty much act like protein folding shortcuts. And so in our example below, what we have is an image for Leventhal's Paradox. And so what you'll see is on the far left over here, what we have is our unfolded protein which has a 100 amino acids in it, a a represents amino acids. And then on the far right, what we have is our native protein structure. And so again, before Leventhal's paradox, the popular belief was that the protein, the unfolded protein, would have to randomly test all of its possible confirmations in a a random trial and error process until it achieved its native structure. And so, you can see all of these different folding pathways and possibilities 100 amino acids, the time that it would a protein with a 100 amino acids, the time that it would take for it to explore all of its possible confirmations was 10 to the 27th years which is a massive massive number in a huge huge amount of time. And so, it's predicted that the age of the entire universe is just 10 to the 9th years. So the time that it would take for a protein with a 100 amino acids to explore all of its possible confirmations is way longer than the length or the age of the entire universe. So there's no way that it could take that long for it to test, for it to achieve its native conformation. And today, we know that it takes the actual time for a protein to fold into its native conformation is actually less than one second. So that's a drastic, a massive difference in time. And so, of course, what that means is that there has to be a predictable folding pathway that, can be achieved to reach the native structure. And, again, this, pathway is dictated by cooperative stepwise interactions between amino acids. And so, this concludes our lesson on Leventhal's paradox and we'll be able to get more practice with these concepts in our practice video. So I'll see you guys there.
4
Problem
Problem
Draw each amino acid & determine which is most likely found in the blue regions of the folded protein below?
A
Asp.
B
Glu.
C
Ile.
D
Gln.
5
Problem
Problem
Which of the following occurs when myoglobin folds into its native conformation?
A
Myoglobin adopts its lowest energy state form.
B
Most of the nonpolar, hydrophobic amino acid residues are found buried in myoglobin's core.
C
Most polar, charged, hydrophilic residues are found on the outside of myoglobin.
D
b and c.
E
All the above.
6
Problem
Problem
In general, which option contains the major cooperative interactions driving spontaneous protein folding?
A
Hydrophobic interactions in the protein core & formation of hydrogen bonds in secondary structures.
B
Formation of salt bridges & disulfide bonds between R-groups that stabilize key interactions.
C
Reduced chain conformational entropy.
D
Restricting surrounding solvent molecules to have less rotational/conformational possibilities.