Polyproline helix

Neuropeptide Y (NPY) is a 36 amino acid polypqrtide with tyrosine residues at both ends of the molecule. It is characterised structurally by a PP-fold consisting of an extended polyproline helix and an a-helix connected by a (3-tum [1]. Based on structural and evolutionary criteria, NPY is closely related to peptide YY (PYY) and pancreatic polypeptide (PP). 

Fillon YA (2005) Cell penetrating agents based on a polyproline helix scaffold. J Am Chem Soc 127 11798-11803... 

A few other helical conformations occur occasionally in globular protein structures. The polyproline helix, of the same sort as one strand out of a collagen structure, has been found in pancreatic trypsin inhibitor (Huber et al., 1971) and in cytochrome c551 (Almassy and Dickerson, 1978). An extended e helix has been described as occurring in chymotrypsin (Srinivasan et al., 1976). In view of the usual variability and irregularity seen in local protein conformation it is unclear that either of these last two helix types is reliably distinguishable from simply an isolated extended strand however, the presence of prolines can justify the designation of polyproline helix. 

Despite different sequences and repetitive motives, all gliadins have the same secondary structure of loose spirals which are a balanced compromise between the p-spiral and poly-L-proline structure (polyproline helix II) (Parrot et al., 2002), the balance is dependent on temperature, type of solvent, and hydration level (Miles et al., 1991). Similar sequences can be found in other proteins, mainly animal proteins such as elastin and collagen, and they are responsible for particular biomechanical properties connected to reverse P-spirals or p-sheet structures (Tatham and Shewry, 2000). 

Although proline cannot participate in a-helical conformations, polypeptides composed only of proline can adopt a different type of helical conformation. This polyproline helix is not stabilized by hydrogen bonding, but rather by the steric mutual repulsion effects of the prolyl side chains. The polyproline helix is more extended than the a helix, with adjacent residues separated along the axis by 0.31 nm. 

Ladokhin, A. S., Selsted, M. E. and White, S. H. (1999) CD spectra of indolicidin antimicrobial peptides suggest turns, not polyproline helix. Biochemistry, 38, 12313-12319. 

Figure 6 shows AFM images of two very similar primary sequences that appear similar after quaternary structure formation and gelation, but one forms a-helices while the other forms P-sheets [44]. Beyond the most common a-helices and -sheets, there are other secondary structures that are less observed in peptide hydrogels [19, 34, 36]. One example is the polyproline helix seen in Fig. 3c, a common secondary structure observed in collagen materials and hydrogels [84]. 

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