TPR Review Exam 1 C/P #56

[basophilic]

Protein folding involves both the formation of secondary and tertiary protein structure to ultimately generate a stereotyped final configuration. What is true of the folding process?

A)A protein with a large number of hydrogen bonds is more likely to have a positive ΔHfolding

B)Multiple equal-energy final structures are possible

C)Buried polar amino acids increase stability

D)The Gfolded is smaller than Gunfolded

I understand D is the best answer and see A is the worst one. However, isn't C also a possibly true statement since transmembrane proteins have polar residues on the inside and nonpolar ones on the outside?

Also for B, I understand that there's only 1 lowest energy conformation, which is why it's false; but you can still have multiple tertiary structures of different/higher energy, right? In other words, it's true that a protein's tertiary structure is determined by its primary one; however, it's not true that a only one tertiary structure corresponds to each primary structure, correct?

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[GoljansRightBicep]

Protein folding involves both the formation of secondary and tertiary protein structure to ultimately generate a stereotyped final configuration. What is true of the folding process?

A)A protein with a large number of hydrogen bonds is more likely to have a positive ΔHfolding

B)Multiple equal-energy final structures are possible

C)Buried polar amino acids increase stability

D)The Gfolded is smaller than Gunfolded

I understand D is the best answer and see A is the worst one. However, isn't C also a possibly true statement since transmembrane proteins have polar residues on the inside and nonpolar ones on the outside?

Also for B, I understand that there's only 1 lowest energy conformation, which is why it's false; but you can still have multiple tertiary structures of different/higher energy, right? In other words, it's true that a protein's tertiary structure is determined by its primary one; however, it's not true that a only one tertiary structure corresponds to each primary structure, correct?

If a protein is in solution (which in the body means an aqueous solution), then you're going to want polar AAs facing out. The example of a transmembrane protein you gave is correct, but this isn't always true for proteins in all situations. Normally transmembrane proteins have their polar AAs facing inwards because they're embedded in a nonpolar membrane and this allows their polar AA residues to H-bond with each other. Also, it can allow substances to pass through them (think of a membrane channel in this case). However, since this is a specific example and is generally not true for all proteins, C is not the best answer. I agree with you that this could be true, most it's certain not the best answer.

Regarding B, I don't know for sure, but what about the example of silent mutations? Imagine replacing an internal Leu with Ile - I bet the protein would have the same conformation since these two AAs are just isomers of each other.

 

[basophilic]

If a protein is in solution (which in the body means an aqueous solution), then you're going to want polar AAs facing out. The example of a transmembrane protein you gave is correct, but this isn't always true for proteins in all situations. Normally transmembrane proteins have their polar AAs facing inwards because they're embedded in a nonpolar membrane and this allows their polar AA residues to H-bond with each other. Also, it can allow substances to pass through them (think of a membrane channel in this case). However, since this is a specific example and is generally not true for all proteins, C is not the best answer. I agree with you that this could be true, most it's certain not the best answer.

Regarding B, I don't know for sure, but what about the example of silent mutations? Imagine replacing an internal Leu with Ile - I bet the protein would have the same conformation since these two AAs are just isomers of each other.

C: so the only reason for eliminating C is that it's a worse answer than D?

B: I disagree; Anfinsen's principle states that each 3D tertiary structure arises uniquely out of the primary sequence; so I wouldn't expect two different primary sequences to have the EXACT same tertiary structure. My question is can each primary structure have multiple tertiary structures (of differing energies)?
Also, you mean a missense mutation? I would expect replacing Leu with Ile would change tertiary structure (though prob not radically)
But yeah silent mutation (I thought silent mutations were those where a base is substituted, but doesn't cause change in primary structure) shouldn't affect primary nor tertiary structure.

 

[GoljansRightBicep]

C: so the only reason for eliminating C is that it's a worse answer than D?

B: I disagree; Anfinsen's principle states that each 3D tertiary structure arises uniquely out of the primary sequence; so I wouldn't expect two different primary sequences to have the EXACT same tertiary structure. My question is can each primary structure have multiple tertiary structures (of differing energies)?
Also, you mean a missense mutation? I would expect replacing Leu with Ile would change tertiary structure (though prob not radically)
But yeah silent mutation (I thought silent mutations were those where a base is substituted, but doesn't cause change in primary structure) shouldn't affect primary nor tertiary structure.

Regarding C, yes that's why it's wrong. Classic case of best answer vs. an answer with a grain of truth in it - so annoying!

B: Sorry, I meant missence mutation, but it looks like you figured that out. Hmm... I'm loving this discourse, you're making me think! Thinking back to when my professor explained the protein folding funnel and the role of Gibb's Free Energy, I do remember him saying that multiple conformations are possible, but that there is a lowest energy conformation... The protein will naturally keep "sampling" all the conformations until it finds the most stable one, heading down the folding funnel. But what about the example of chaperones, where a protein won't reach its lowest energy state fast enough? They're basically enzymes for protein folding, so wouldn't the product and reactant of that catalysis be an example of two conformations like you're talking about? I'm obviously just spit-balling here since I don't know a definitive answer. I'm very intrigued!