Pore-forming proteins (PFPs) and small antimicrobial peptides (AMPs) represent a large family of molecules with the common ability to punch holes in cell membranes to alter their permeability. They play a fundamental role as infectious bacteria’s defensive tools against host’s immune system and as executors of endogenous machineries of regulated cell death in eukaryotic cells. Despite being highly divergent in primary sequence and 3D structure, specific folds of pore-forming domains have been conserved. In fact, pore formation is considered an ancient mechanism that takes place through a general multistep process involving: membrane partitioning and insertion, oligomerization and pore formation. However, different PFPs and AMPs assemble and form pores following different mechanisms that could end up either in the formation of protein-lined or protein-lipid pores. In this review, we analyze the current findings in the mechanism of action of different PFPs and AMPs that support a wide role of membrane pore formation in nature. We also provide the newest insights into the development of state-of-art techniques that have facilitated the characterization of membrane pores. To understand the physiological role of these peptides/proteins or develop clinical applications, it is essential to uncover the molecular mechanism of how they perforate membranes.

成孔蛋白 (PFP​​) 和小抗菌肽 (AMP) 代表了一大类分子，它们具有在细胞膜上打孔以改变其渗透性的共同能力。它们作为感染性细菌抵御宿主免疫系统的防御工具和真核细胞中调节细胞死亡的内源性机制的执行者发挥着重要作用。尽管在一级序列和 3D 结构上存在很大差异，但成孔结构域的特定折叠是保守的。事实上，孔的形成被认为是一种古老的机制，它通过一般的多步骤过程发生，包括：膜分配和插入、低聚和孔形成。然而，不同的 PFP 和 AMP 按照不同的机制组装并形成孔，这些机制可能最终形成蛋白质衬里或蛋白质脂质孔。在这篇综述中，我们分析了目前在不同 PFP 和 AMP 的作用机制中的发现，这些 PFP 和 AMP 支持自然界中膜孔形成的广泛作用。我们还提供了对促进膜孔表征的最先进技术发展的最新见解。要了解这些肽/蛋白质的生理作用或开发临床应用，必须揭示它们如何穿透膜的分子机制。我们还提供了对促进膜孔表征的最先进技术发展的最新见解。要了解这些肽/蛋白质的生理作用或开发临床应用，必须揭示它们如何穿透膜的分子机制。我们还提供了对促进膜孔表征的最先进技术发展的最新见解。要了解这些肽/蛋白质的生理作用或开发临床应用，必须揭示它们如何穿透膜的分子机制。