Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
Sydney Medical School-Westmead, University of Sydney, Sydney, New South Wales, Australia.
Cell Microbiol. 2021 Jun;23(6):e13325. doi: 10.1111/cmi.13325. Epub 2021 Mar 25.
Inositol polyphosphates (IPs) and inositol pyrophosphates (PP-IPs) regulate diverse cellular processes in eukaryotic cells. IPs and PP-IPs are highly negatively charged and exert their biological effects by interacting with specific protein targets. Studies performed predominantly in mammalian cells and model yeasts have shown that IPs and PP-IPs modulate target function through allosteric regulation, by promoting intra- and intermolecular stabilization and, in the case of PP-IPs, by donating a phosphate from their pyrophosphate (PP) group to the target protein. Technological advances in genetics have extended studies of IP function to microbial pathogens and demonstrated that disrupting PP-IP biosynthesis and PP-IP-protein interaction has a profound impact on pathogenicity. This review summarises the complexity of IP-mediated regulation in eukaryotes, including microbial pathogens. It also highlights examples of poor conservation of IP-protein interaction outcome despite the presence of conserved IP-binding domains in eukaryotic proteomes.
肌醇多磷酸盐（IPs）和肌醇焦磷酸盐（PP-IPs）在真核细胞中调节多种细胞过程。IPs 和 PP-IPs 带高度负电荷，通过与特定的蛋白质靶标相互作用发挥其生物学效应。主要在哺乳动物细胞和模式酵母中进行的研究表明，IPs 和 PP-IPs 通过别构调节来调节靶标功能，通过促进分子内和分子间的稳定化，并且在 PP-IPs 的情况下，通过从其焦磷酸盐（PP）基团向靶标蛋白捐赠一个磷酸来调节。遗传学技术的进步将 IP 功能的研究扩展到了微生物病原体，并证明了破坏 PP-IP 生物合成和 PP-IP-蛋白质相互作用对致病性有深远的影响。本综述总结了真核生物中 IP 介导的调节的复杂性，包括微生物病原体。它还强调了尽管真核生物蛋白质组中存在保守的 IP 结合结构域，但 IP-蛋白质相互作用的结果并不保守。
