Triglycine (GGG) Adopts a Polyproline II (pPII) Conformation in Its Hydrated Crystal Form: Revealing the Role of Water in Peptide Crystallization

Polyproline II (pPII) is a left-handed
31-helix conformation,
which has been observed to be the most abundant secondary structure
in unfolded peptides and proteins compared to α-helix and β-sheet.
Although pPII has been reported as the most stable conformation for
several unfolded short chain peptides in aqueous solution, it is rarely
observed in their solid state. Here, we show for the first time a
glycine homopeptide (gly-gly-gly) adopting the pPII conformation in
its crystalline dihydrate structure. The single crystal X-ray structure
with molecular dynamic simulation suggests that a network of water
and the charged carboxylate group is critical in stabilizing the pPII
conformation in solid state, offering an insight into the structures
of unfolded regions of proteins and the role of water in peptide crystallization.