Properties of the PPII Helix and Principles of PRM Recognition

A common property of all PRMs is that they preferentially form a left-handed poly-proline type-II (PPII) helix with an overall shape resembling a triangular prism (Kay et al. 2000). This structural element has a helical pitch of 9.3 Â, three residues per turn, and F and Y angles centered around -75° and 145°, respectively (Bochicchio and Tamburro 2002; Cubellis et al. 2005). The PPII helix is characterized by a complete lack of main-chain hydrogen bonding patterns that are commonly used to identify other secondary structures, such as a-helices or P-sheets. This property is the reason for problems in distinguishing PPII helices from unfolded conformations using NMR spectroscopy. However, other spectroscopic techniques, such as CD spectroscopy, indicate that the PPII helix is the common conformation of the unbound state (Tiffany and Krimm 1968). Although proline is common in PPII helices, PPII helices without proline were found in 46% of the total identified proteins taken from the HOMSTRAD database (Mizuguchi et al. 1998; de Bakker et al. 2001). Most amino acids are accepted in the context of the PPII helix, though glycine and aromatic amino acids have low propensities to be part of this structure (Cubellis et al. 2005). Results of a theoretical study shed light on the forces stabilizing the PPII helix (Sreerama and Woody 1999). A PPII, an a-helix and a P-strand were the starting conformations for a molecular dynamics study of an (Ala)8-peptide in water. Only the a-helix remained intact during the simulation, while the others showed more flexibility due to the lack of stabilizing intramolecular hydrogen bonds. The PPII conformation was found to be populated twice as frequently as the P-strand. In fact, for both conformations the water molecules form hydrogen bonds to the peptide backbone and to one another, thus constituting a bridge connecting two backbone atoms of the peptide. Interestingly, only in the case of the PPII conformations were water molecules able to connect two consecutive oxygen atoms of the backbone. This clearly suggests that water can be important in stabilizing the PPII structure. It was shown that PPII helices disrupt the structural arrangement of water molecules to a smaller degree than a-helices and P-sheets. Thus, PPII helix formation appears to be entropically driven (Kentsis et al. 2004; Mezei et al. 2004). The tendency of the PPII structure to form favorable contacts with water is potentially responsible for the finding that PPII helices within proteins are frequently solvent-exposed (Adzhubei and Sternberg 1993). Taking into account that PPII conformers contain an increased number of non-satisfied hydrogen bond donors and acceptors in comparison to a-helices and P-strands, the PPII helix is well suited to take part in protein-protein interactions.

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