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Protein translocation through α-helical channels and insertases
Structure ( IF 4.4 ) Pub Date : 2024-11-25 , DOI: 10.1016/j.str.2024.10.032
Jingxia Chen, Xueyin Zhou, Yuqi Yang, Long Li

Protein translocation systems are essential for distributing proteins across various lipid membranes in cells. Cellular membranes, such as the endoplasmic reticulum (ER) membrane and mitochondrial inner membrane, require highly regulated protein translocation machineries that specifically allow the passage of protein polypeptides while blocking smaller molecules like ions and water. Key translocation systems include the Sec translocation channel, the protein insertases of the Oxa1 superfamily, and the translocases of the mitochondrial inner membrane (TIM). These machineries utilize different mechanisms to create pathways for proteins to move across membranes while preventing ion leakage during the dynamic translocation processes. In this review, we highlight recent advances in our understanding of these α-helical translocation machineries and examine their structures, mechanisms, and regulation. We also discuss the therapeutic potential of these translocation pathways and summarize the progress in drug development targeting these systems for treating diseases.

中文翻译:


蛋白质通过 α-螺旋通道和插入酶易位



蛋白质易位系统对于将蛋白质分布在细胞中的各种脂质膜上至关重要。细胞膜,如内质网 (ER) 膜和线粒体内膜,需要高度调节的蛋白质易位机制,这些机制专门允许蛋白质多肽通过,同时阻断离子和水等较小的分子。关键的易位系统包括 Sec 易位通道、Oxa1 超家族的蛋白质插入酶和线粒体内膜 (TIM) 的易位酶。这些机制利用不同的机制为蛋白质创建跨膜移动的途径,同时防止动态转位过程中的离子泄漏。在这篇综述中,我们重点介绍了我们对这些 α 螺旋易位机制的理解的最新进展,并研究了它们的结构、机制和调节。我们还讨论了这些易位途径的治疗潜力,并总结了针对这些系统治疗疾病的药物开发进展。
更新日期:2024-11-25
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