Question on EK in-class exam 1 Biology

[divinelyawesome]

Passage 1. question 3. The answer is C (the long answer). I picked this one by process of elimination, but its logic does not make sense to me. what does the possible combination of bonding have to do with anything? When a protein is denatured, its primary structure stays intact. So, the sequence is already predetermined right? We are only dealing with one long protein sequence right? Or, the combination mentioned is taking account of the fact that the genetic code is degenerative. In which case one AA can have different codon combinations. I'm really confused here. I don't know if it's because i'm looking at proteins without associating them to nucleic acids.

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[labqi]

Can you post the question?

 

[divinelyawesome]

Which of the following is the best explanation for why attempts at predicting protein configuration based upon amino acid sequence have been unsucceful?
A. it is impossible to know the amino acid sequence of a protein without knowing the DNA nucleotide sequence.
B. Enzyme and chaperones help to determine the three dimensional shape of the protein.
C. Three dimensional shape of a protein is bases upon hydrogen and disulfide bonding between amino acids, and the number of possible combinations of bonding amino acids makes prediction difficult.
D. The amino acid sequence of the same protein may vary slightly from one sample to the next.

The correct answer is C.

Thanks for your help.

 

[DrknoSDN]

When a protein is denatured, its primary structure stays intact. So, the sequence is already predetermined right? We are only dealing with one long protein sequence right? Or, the combination mentioned is taking account of the fact that the genetic code is degenerative. In which case one AA can have different codon combinations. I'm really confused here. I don't know if it's because i'm looking at proteins without associating them to nucleic acids.

When the questions asks why predicting protein configuration [is difficult] based on amino acid sequence. It is asking about the 3d protein structure (secondary, and tertiary) in this case. So a denatured protein wouldn't do any good because you can't predict how it folds from primary structure.

When it says " the number of possible combinations of bonding amino acids" it is not talking about degenerate code. You know the amino acid sequence so DNA or mRNA are not a factor. Predicting the shape of a protein is difficult because there are a lot of different way that the residues can bond to each other.

Example: If you just had 4 cysteines in a protein They could form disulfide bonds between:
1-2
1-3
1-4
2-3
2-4
3-4
1-2 and 3-4
1-3 and 2-4
1-4 and 2-3
etc....

That's not even counting the H-bonding, so if you include hydrogen bonding the number of combinations of bonds in a protein sequence that alter protein structure becomes impressively large.

Also not sure about the validity of the source but (http://www.weizmann.ac.il/plants/Milo/images/proteinSize120116Clean.pdf) shows that the average protein length in humans is 375 amino acids so you could expect more like 18-20 cysteines in an average protein making it harder to know where/if disulfide bonds form.

 

[Czarcasm]

For globular proteins, the final protein conformation in aqueous solution is primarily drive by the hydrophobic effect which indirectly aids cysteine residues (provided they're available) to combine together in an oxidizing environment. Other van der waals, including hydrogen bonding, also facilitate the formation of these bonds and the final structure of the protein.

If you still want some insight, check out Anfinsen's experiment on protein folding and I think you'll understand this a little better. This was a major finding that essentially proved both how and why proteins fold and that the process occurs spontaneously in solution to produce a single functional protein (...for the reasons I basically eluded to earlier).

 

[DrknoSDN]

If you still want some insight, check out Anfinsen's experiment on protein folding and I think you'll understand this a little better. This was a major finding that essentially proved both how and why proteins fold and that the process occurs spontaneously in solution to produce a single functional protein (...for the reasons I basically eluded to earlier).

I don't believe all proteins will spontaneously fold correctly in solution. Folding that initially requires chaperon proteins will often not reform correctly after being denatured. The product being a non-functional protein.

 

[Czarcasm]

I don't believe all proteins will spontaneously fold correctly in solution. Folding that initially requires chaperon proteins will often not reform correctly after being denatured. The product being a non-functional protein.

We're both correct. In my previous explanation, I was referring to a process in vitro. However, in vivo, as you described the process is facilitated by proteins including chaperones (as well as PDI which aids in forming disulfide bridges). Chaperones assist proteins in folding to their proper three dimensional shape by preventing these improper foldings. This is especially important in cells were the polypeptide is being synthesized progressively (in comparison to an in vitro process: a fully unfolded polypeptide). The purpose of the experiment was mainly to demonstrate that the primary amino acid sequence dictates the tertiary structure of a protein. In cells however, we see that it's a little bit more complicated than that.