Polyproline-II helix in proteins: structure and function

Abstract

The poly-l-proline type II (PPII) helix in recent years has emerged clearly as a structural class not only of fibrillar proteins (in collagen, PPII is a dominant conformation) but also of the folded and unfolded proteins. Although much less abundant in folded proteins than the α-helix and β-structure, the left-handed, extended PPII helix represents the only frequently occurring regular structure apart from these two structure classes. Natively unfolded proteins have a high content of the PPII helices identified by spectroscopic methods. Apart from the structural function, PPII is favorable for protein-protein and protein-nucleic acid interactions and plays a major role in signal transduction and protein complex assembly, as this structure is often found in binding sites, specifically binding sites of widely spread SH3 domains. PPII helices do not necessarily contain proline, but proline has high PPII propensity. Commonly occurring proline-rich regions, serving as recognition sites, are likely to have PPII structure. PPII helices are involved in transcription, cell motility, self-assembly, elasticity, and bacterial and viral pathogenesis, and has an important structural role in amyloidogenic proteins. However, PPII helices are not always assigned in experimentally solved structures, and they are rarely used in protein structure modeling. We aim to give an overview of this structural class and of the place it holds in our current understanding of protein structure and function. This review is subdivided into three main parts: the first part covers PPII helices in unfolded peptides and proteins, the second part includes studies of the PPII helices in folded proteins, and the third part discusses the functional role of the PPII.