nbme21/Block 3/Question#28

A 1-year-old girl is admitted to the hospital ...

Disruption of the secondary structure of collagen molecules

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submitted by cellgamesgojan(3),

I figured, glycine-X-Y is technically considered a “primary amino acid structure of a protein” since the definition of a Primary structure of a protein is “a linear chain of amino acids.” If you mess with the Primary structure, as in the question stem, you cannot form the Secondary structure of the protein, which is determined by the hydrogen-bonding which occurs between the peptide backbone, independent of the R groups. I hope this made sense.

From wikipedia: “Secondary structure is formally defined by the pattern of hydrogen bonds between the amino hydrogen and carboxyl oxygen atoms in the peptide backbone.” (emphasis mine)

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submitted by porky_pork_chop(0),

Why would it be a disruption of the secondary structure of collagen molecules? I thought to form the tropocollagen triple helix hydrogen bonds are needed; and FA says failure of formation of the triple helix results in Osteogenesis Imperfecta.

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submitted by wasabilateral(0),

I think it has something to do with glycine (due to its small size it can fit in many places where other amino acids can not and hence it provides “structural compactness” to the collagen, i.e. put a kink in the alpha helix). If glycine is misplaced by something else, I don’t think pro-collagen can form its correct secondary structure.

jotajota94  True! also, glycine is 1/3 of collagen alfa chains, so it makes sense that substitution with alanine (which is much bigger) would lead to disruption in the alpha helix formation.

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submitted by drdoom(14),

Here’s one way to process-of-eliminate “decreased hydrogen-bond formation”: I’m not a big fan of this line of reasoning, but technically alanine as a side group has more hydrogens* for potential hydrogen bonding than glycine:

alanine: —CH3
glycine: —H

So, “technically,” alanine would permit more hydrogen-bond formation, which might allow you to eliminate that choice.

That said, it seems almost impossible to rule out (without very technical knowledge or some provided experimental data) that the slightly larger alanine does not impair hydrogen bonding between collagen molecules via steric (spatial) interference. In simpler terms, since alanine is larger, you would think that it must somehow interfere with the hydrogen-bonding that occurs with the wild-type glycine.

*Strictly speaking, it’s not the number of hydrogens but also the strength of the dipole that facilitates hydrogen bonding: a hydrogen bound to a strongly electronegative molecule like fluorine will “appear” more positive and, thus, hydrogen-bond more strongly with a nearby oxygen (compared with a hydrogen connected to carbon, for example).

Further reading:

  1. https://www.chem.purdue.edu/gchelp/liquids/hbond.html