Multidomain Peptidyl Prolyl cis/trans Isomerases

Background: Peptidyl prolyl cis/trans isomerases (PPIases) assist the folding and restructuring of client proteins by catalysis of the slow rotational motion of peptide bonds preceding a proline residue. Catalysis is performed by relatively small, distinct protein domains of 10 to 18 kDa for all PPIase families. PPIases are involved in a wide variety of physiological and pathophysiological processes like signal transduction, cell differentiation, apoptosis as well as viral, bacterial and parasitic infection. Scope of review: There are multidomain PPIases consisting of one to up to four catalytic domains of the respective PPIase family supplemented by N- or C-terminal extensions. This review examines the biochemical and functional properties of the members of the PPIase class of enzymes which contain additional protein domains with defined biochemical functions. Major conclusions: The versatile domain architecture of multidomain PPIases is important for the control of enzyme specificity and organelle-specific targeting, the establishment of molecular connections and hence the coordination of PPIase functions across the cellular network. General significance: Accessory domains covalently linked to a PPIase domain supply an additional layer of control to the catalysis of prolyl isomerization in specific client proteins. Understanding these control mechanisms will provide new insights into the physiological mode of action of the multidomain PPIases and their ability to form therapeutic targets. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets. (C) 2014 Elsevier B.V. All rights reserved.