β-Barrel pore-forming toxins:: Intriguing dimorphic proteins
β-Barrel pore-forming toxins:: Intriguing dimorphic proteins
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DOI：
10.1021/bi0155394
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发表时间：
2001-08-07
期刊：
影响因子：
2.9
通讯作者：
Johnson, AE
中科院分区：
文献类型：
--
作者：
Heuck, AP;Tweten, RK;Johnson, AE
许多细菌分泌具有内在特性的多肽，这些特性产生非常广泛的稳定结构状态。具体地，这些多肽可以作为水溶性单体或作为多聚体整合膜蛋白存在。此外，从水中的稳定折叠状态转化为膜内不同的稳定折叠状态的能力也是多肽的固有性质。这种转化是自发的，尽管它是由与膜表面的特定蛋白质、脂质和/或碳水化合物的相互作用触发的，但多肽插入膜中的过程不需要其他蛋白质作为伴侣或能量转换器的帮助。因此，蛋白质生物化学家、蛋白质折叠器、结构生物学家和其他人对这些多肽的结构二态性感兴趣，而临床医生、微生物学家和其他人则专注于这些有趣的结构特性的功能分支。因为这些蛋白质是细菌的成孔毒素，它们的作用是破坏或渗透哺乳动物细胞，干扰它们的功能，在几乎所有情况下，蛋白质插入细胞膜是一个高度调节的过程，除了插入的多肽外，还涉及多种蛋白质。例如，在真核细胞中，膜蛋白整合到内质网（ER）的膜中通常需要复杂的分子机制（称为转位子）和一系列协调的核糖体和转位子相互作用和运动来完成整合（1）。类似的蛋白质介导的过程影响膜蛋白插入线粒体膜（2），叶绿体膜（3，4）和细菌膜（3，5）。这些过程通常还需要伴侣蛋白或机制（例如，通过真核信号识别颗粒的翻译停滞）以维持多肽处于可插入状态（1-5）。
Many bacteria secrete polypeptides with intrinsic properties that generate a remarkably wide range of stable structural states. Specifically, these polypeptides can exist either as a water-soluble monomer or as a multimeric integral membrane protein. Furthermore, the ability to convert from a stable folded state in water to a different stable folded state inside a membrane is also an intrinsic property of the polypeptide. This conversion is spontaneous, and though it is triggered by an interaction with a specific protein, lipid, and/or carbohydrate at the membrane surface, the insertion of the polypeptide into the membrane proceeds without the assistance of other proteins as chaperones or energy transducers. Protein biochemists, protein folders, structural biologists, and others are therefore intrigued by the structural dimorphism of these polypeptides, while clinicians, microbiologists, and others are focused on the functional ramifications of these interesting structural properties. For these proteins are bacterial pore-forming toxins, and their purpose is to damage or infiltrate mammalian cells and interfere with their function.The insertion of proteins into membranes is, in nearly all cases, a highly regulated process that involves multiple proteins besides the polypeptide being inserted. For example, membrane protein integration into the membrane of the endoplasmic reticulum (ER) in eukaryotic cells usually requires complex molecular machinery (termed the translocon) and a series of coordinated ribosome and translocon interactions and movements to accomplish integration (1). Similar protein-mediated processes effect the insertion of membrane proteins into mitochondrial membranes (2), chloroplast membranes (3, 4), and bacterial membranes (3, 5). These processes also usually require a chaperone (s) or mechanism (eg, translational arrest by eukaryotic signal recognition particle) to maintain the polypeptide in an insertion-competent state (1-5).