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.

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)

Due to glycine's small size, it creates "kinks" in the amino acid sequence. These kinks are needed to correctly form the secondary structure.

Other answers:

• "weakened interaction between collagen and proteoglycan" - collagen + proteoglycan = cartillage. The question stem mentions many defects in bONE (type I collagen) but no mention of defects in carTWOllage (type II collagen)

ok guys and i quote from https://www.orthobullets.com/pediatrics/4102/osteogenesis-imperfecta

"90% have an identifiable genetic mutation COL 1A1 and COL 1A2
causes abnormal collagen cross-linking via a glycine substitution in the procollagen molecule "

which means that OI has a glycine substitution and therfore its unable to form a secondary sturucture.

I might be overthinking it but, H bond formation of aa's makes the secondary structure of the protein (collagen in this case). The Gly to Ala substitution does result in less H bond formation, but of individual aa's not between collagen molecules (that might be more for quaternary structure)

Gly is polar, Alanine is nonpolar and hydrophobic. Missense nonconservative mutation. These AAs have different chemical properties which lead to disrupted protein folding (secondary structure). Similar to Glu - Val substitution in Sickle Cell Disease.

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.

the way I thought about it, is that the Osteogenesis Imperfecta results in defective osteoid production which is a secondary structure to collagen synthesis

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.

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*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