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Why do large, aromatic residues prefer beta-pleated sheets?
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Kathryn Barker
Why do large, aromatic residues prefer beta-pleated sheets?
This table is from the Wikipedia page for α-helix:
As you can see aromatics are not the worst offenders. In fact, barring proline (whose backbone torsion angles are unsuited to helices), Gly is the worst offender. A likely reason for this is Gly being too flexible i.e. its small side chain H allows it to adopt backbone torsion angles unsuited for α-helix.
As another example let's look at silk, an extended anti parallel β-sheet structure, from libretexts.
As you can see, the small side chains of Ala and Gly in fact allows the β-strands to come close enough to form backbone hydrogen bonds. In fact, from the same reference I quote - "Unlike the α helix, though, the side chains are squeezed rather close together in a pleated-sheet arrangement. In consequence very bulky side chains make the structure unstable."
So it is not entirely true that aromatic amino acids prefer pleated β-sheets.
So what are we missing? We are missing the chemical environment in which the the amino acid residues are placed. Remember, most of the propensity charts we look at are average propensities across known protein structures. In a specific protein, its specific chemical context can radically change the secondary structure propensities.
This table is from the Wikipedia page for α-helix:
As you can see aromatics are not the worst offenders. In fact, barring proline (whose backbone torsion angles are unsuited to helices), Gly is the worst offender. A likely reason for this is Gly being too flexible i.e. its small side chain H allows it to adopt backbone torsion angles unsuited for α-helix.
As another example let's look at silk, an extended anti parallel β-sheet structure, from libretexts.
As you can see, the small side chains of Ala and Gly in fact allows the β-strands to come close enough to form backbone hydrogen bonds. In fact, from the same reference I quote - "Unlike the α helix, though, the side chains are squeezed rather close together in a pleated-sheet arrangement. In consequence very bulky side chains make the structure unstable."
So it is not entirely true that aromatic amino acids prefer pleated β-sheets.
So what are we missing? We are missing the chemical environment in which the the amino acid residues are placed. Remember, most of the propensity charts we look at are average propensities across known protein structures. In a specific protein, its specific chemical context can radically change the secondary structure propensities.
I am aware of the effects of proline and glycine on secondary protein structures, but didn't find it relevant to the question, but thanks for further clarifying it anyways. Your example of silk is really insightful as well. However, I am still wondering why the aromatic residues have a higher average propensity (through various chemical contexts, like you mentioned); at least, relatively higher than smaller residues like on alanine, glutamate etc.More
@chematwork The strength of a hydrogen bond depends on the distance between the bond donor and acceptor, electronegativities of the atoms and the angle donor--H--acceptor. So if you have bulky side chain residues in beta sheets (e.g. a benzene ring is around 4 A in length) you can see that they will weaken hydrogen bonds as the distances between the bond donor and acceptor will increase.More
@chematwork — This answer is far better than yours because it exposes the fundamental fallacy of “the average beta sheet” of your question. The average human being has one ovary and one testicle. Alpha helices do allow certain general principles, but the variety of conformations of beta-sheets in proteins, and the variety of their environments preclude all but the most superficial statements. When few structures were known, this sort of thing was all one could say. Fifty years have passed since then.More
@David I checked the beta sheet propensities of aromatic side chains and while they have high average propensities, I seriously doubt a polypeptide of only aromatic side chains will show a tendency to form a beta sheet. Sadly I don't have enough expertise to run MD simulations to check this.More
Also, I am confused when you say that alanine and glycine allow the beta-pleated sheets to come close enough to form backbone hydrogen bonds. Aren't backbone hydrogen bonds formed despite the residues (excluding proline)? Do you mean the hydrogen bonds will be stronger as they are closer together? In antiparallel beta sheets the amide hydrogen and carbonyl oxygen are pointing directly at each other, so I doubt they will not form bonds even if there is more space in between.More
This table is from the Wikipedia page for α-helix:
As you can see aromatics are not the worst offenders. In fact, barring proline (whose backbone torsion angles are unsuited to helices), Gly is the worst offender. A likely reason for this is Gly being too flexible i.e. its small side chain H allows it to adopt backbone torsion angles unsuited for α-helix.
As another example let's look at silk, an extended anti parallel β-sheet structure, from libretexts.
As you can see, the small side chains of Ala and Gly in fact allows the β-strands to come close enough to form backbone hydrogen bonds. In fact, from the same reference I quote - "Unlike the α helix, though, the side chains are squeezed rather close together in a pleated-sheet arrangement. In consequence very bulky side chains make the structure unstable."
So it is not entirely true that aromatic amino acids prefer pleated β-sheets.
So what are we missing? We are missing the chemical environment in which the the amino acid residues are placed. Remember, most of the propensity charts we look at are average propensities across known protein structures. In a specific protein, its specific chemical context can radically change the secondary structure propensities.
This table is from the Wikipedia page for α-helix:
As you can see aromatics are not the worst offenders. In fact, barring proline (whose backbone torsion angles are unsuited to helices), Gly is the worst offender. A likely reason for this is Gly being too flexible i.e. its small side chain H allows it to adopt backbone torsion angles unsuited for α-helix.
As another example let's look at silk, an extended anti parallel β-sheet structure, from libretexts.
As you can see, the small side chains of Ala and Gly in fact allows the β-strands to come close enough to form backbone hydrogen bonds. In fact, from the same reference I quote - "Unlike the α helix, though, the side chains are squeezed rather close together in a pleated-sheet arrangement. In consequence very bulky side chains make the structure unstable."
So it is not entirely true that aromatic amino acids prefer pleated β-sheets.
So what are we missing? We are missing the chemical environment in which the the amino acid residues are placed. Remember, most of the propensity charts we look at are average propensities across known protein structures. In a specific protein, its specific chemical context can radically change the secondary structure propensities.
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