Ünal Can M, Steinert Michael
Türk-Alman Üniversitesi, Fen Fakültesi, Istanbul, Turkey Technische Universität Braunschweig, Institut für Mikrobiologie, Braunschweig, Germany
Technische Universität Braunschweig, Institut für Mikrobiologie, Braunschweig, Germany Helmholtz Centre for Infection Research, Braunschweig, Germany
Microbiol Mol Biol Rev. 2014 Sep;78(3):544-71. doi: 10.1128/MMBR.00015-14.
Initially discovered in the context of immunomodulation, peptidyl-prolyl cis/trans isomerases (PPIases) were soon identified as enzymes catalyzing the rate-limiting protein folding step at peptidyl bonds preceding proline residues. Intense searches revealed that PPIases are a superfamily of proteins consisting of three structurally distinguishable families with representatives in every described species of prokaryote and eukaryote and, recently, even in some giant viruses. Despite the clear-cut enzymatic activity and ubiquitous distribution of PPIases, reports on solely PPIase-dependent biological roles remain scarce. Nevertheless, they have been found to be involved in a plethora of biological processes, such as gene expression, signal transduction, protein secretion, development, and tissue regeneration, underscoring their general importance. Hence, it is not surprising that PPIases have also been identified as virulence-associated proteins. The extent of contribution to virulence is highly variable and dependent on the pleiotropic roles of a single PPIase in the respective pathogen. The main objective of this review is to discuss this variety in virulence-related bacterial and protozoan PPIases as well as the involvement of host PPIases in infectious processes. Moreover, a special focus is given to Legionella pneumophila macrophage infectivity potentiator (Mip) and Mip-like PPIases of other pathogens, as the best-characterized virulence-related representatives of this family. Finally, the potential of PPIases as alternative drug targets and first tangible results are highlighted.
肽基脯氨酰顺/反异构酶（PPIases）最初是在免疫调节的背景下被发现的，很快就被鉴定为在脯氨酸残基之前的肽键处催化限速蛋白质折叠步骤的酶。深入研究发现，PPIases是一个蛋白质超家族，由三个结构上可区分的家族组成，在每种已描述的原核生物和真核生物中都有代表，最近甚至在一些巨型病毒中也有发现。尽管PPIases具有明确的酶活性且分布广泛，但关于仅依赖PPIase的生物学作用的报道仍然很少。然而，人们发现它们参与了大量的生物学过程，如基因表达、信号转导、蛋白质分泌、发育和组织再生，这突出了它们的普遍重要性。因此，PPIases也被鉴定为与毒力相关的蛋白质也就不足为奇了。其对毒力的贡献程度差异很大，并且取决于单个PPIase在各自病原体中的多效性作用。本综述的主要目的是讨论与毒力相关的细菌和原生动物PPIases的这种多样性，以及宿主PPIases在感染过程中的参与情况。此外，特别关注嗜肺军团菌巨噬细胞感染增强剂（Mip）和其他病原体的Mip样PPIases，它们是该家族中特征最明确的与毒力相关的代表。最后，强调了PPIases作为替代药物靶点的潜力和首批切实成果。
