Sibley L David
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Biochim Biophys Acta. 2013 Dec;1828(12):2908-15. doi: 10.1016/j.bbamem.2013.04.017.
Intramembrane proteolysis is widely conserved throughout different forms of life, with three major types of proteases being known for their ability to cleave peptide bonds directly within the transmembrane domains of their substrates. Although intramembrane proteases have been extensively studied in humans and model organisms, they have only more recently been investigated in protozoan parasites, where they turn out to play important and sometimes unexpected roles. Signal peptide peptidases are involved in endoplasmic reticulum (ER) quality control and signal peptide degradation from exported proteins. Recent studies suggest that repurposing inhibitors developed for blocking presenilins may be useful for inhibiting the growth of Plasmodium, and possibly other protozoan parasites, by blocking signal peptide peptidases. Rhomboid proteases, originally described in the fly, are also widespread in parasites, and are especially expanded in apicomplexans. Their study in parasites has revealed novel roles that expand our understanding of how these proteases function. Within this diverse group of parasites, rhomboid proteases contribute to processing of adhesins involved in attachment, invasion, intracellular replication, phagocytosis, and immune evasion, placing them at the vertex of host-parasite interactions. This article is part of a Special Issue entitled: Intramembrane Proteases.
膜内蛋白水解在不同生命形式中广泛存在，已知有三种主要类型的蛋白酶能够直接在其底物的跨膜结构域内切割肽键。尽管膜内蛋白酶已在人类和模式生物中得到广泛研究，但直到最近才在原生动物寄生虫中进行研究，结果发现它们在其中发挥着重要且有时意想不到的作用。信号肽肽酶参与内质网（ER）质量控制和输出蛋白的信号肽降解。最近的研究表明，重新利用开发用于阻断早老素的抑制剂可能有助于通过阻断信号肽肽酶来抑制疟原虫以及可能的其他原生动物寄生虫的生长。最初在果蝇中发现的类菱形蛋白酶在寄生虫中也广泛存在，在顶复门寄生虫中尤其丰富。对它们在寄生虫中的研究揭示了一些新作用，扩展了我们对这些蛋白酶功能的理解。在这群多样的寄生虫中，类菱形蛋白酶有助于处理参与附着、入侵、细胞内复制、吞噬作用和免疫逃避的黏附素，使它们处于宿主 - 寄生虫相互作用的关键位置。本文是名为“膜内蛋白酶”的特刊的一部分。
