Waksman Institute of Microbiology, Rutgers University, Piscataway, New Jersey, USA.
Department of Genetics, Rutgers University, Piscataway, New Jersey, USA.
J Bacteriol. 2022 Jan 18;204(1):e0034421. doi: 10.1128/JB.00344-21. Epub 2021 Sep 13.
Small membrane proteins represent a subset of recently discovered small proteins (≤100 amino acids), which are a ubiquitous class of emerging regulators underlying bacterial adaptation to environmental stressors. Until relatively recently, small open reading frames encoding these proteins were not designated genes in genome annotations. Therefore, our understanding of small protein biology was primarily limited to a few candidates associated with previously characterized larger partner proteins. Following the first systematic analyses of small proteins in Escherichia coli over a decade ago, numerous small proteins across different bacteria have been uncovered. An estimated one-third of these newly discovered proteins in are localized to the cell membrane, where they may interact with distinct groups of membrane proteins, such as signal receptors, transporters, and enzymes, and affect their activities. Recently, there has been considerable progress in functionally characterizing small membrane protein regulators aided by innovative tools adapted specifically to study small proteins. Our review covers prototypical proteins that modulate a broad range of cellular processes, such as transport, signal transduction, stress response, respiration, cell division, sporulation, and membrane stability. Thus, small membrane proteins represent a versatile group of physiology regulators at the membrane and the whole cell. Additionally, small membrane proteins have the potential for clinical applications, where some of the proteins may act as antibacterial agents themselves while others serve as alternative drug targets for the development of novel antimicrobials.
小膜蛋白是最近发现的小蛋白（≤100 个氨基酸）的一个子集，它们是一类普遍存在的新兴调节剂，在细菌适应环境胁迫中起着重要作用。直到最近，这些蛋白的小开放阅读框编码的基因在基因组注释中才被指定为基因。因此，我们对小蛋白生物学的理解主要局限于与先前表征的较大伴侣蛋白相关的少数几个候选蛋白。十多年前首次对大肠杆菌中的小蛋白进行系统分析后，在不同的细菌中发现了许多小蛋白。据估计，这些新发现的蛋白中约有三分之一位于细胞膜上，在那里它们可能与不同的膜蛋白群相互作用，如信号受体、转运蛋白和酶，并影响它们的活性。最近，在专门用于研究小蛋白的创新工具的辅助下，对小膜蛋白调节剂的功能特性进行了相当大的研究。我们的综述涵盖了调节广泛细胞过程的典型蛋白，如运输、信号转导、应激反应、呼吸、细胞分裂、孢子形成和膜稳定性。因此，小膜蛋白是膜和整个细胞中具有多功能的生理调节剂。此外，小膜蛋白具有临床应用的潜力，其中一些蛋白本身可能作为抗菌剂，而另一些则可以作为开发新型抗菌药物的替代药物靶点。
