Cryo-electron Microscopic Analysis of Single-Pass Transmembrane Receptors,Chemical Reviews

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Cryo-electron Microscopic Analysis of Single-Pass Transmembrane Receptors
Chemical Reviews ( IF 51.4 ) Pub Date : 2022-06-17 , DOI: 10.1021/acs.chemrev.1c01035
Kai Cai ₁ , Xuewu Zhang _{1,

2} , Xiao-Chen Bai _{1,

3}

Affiliation

Single-pass transmembrane receptors (SPTMRs) represent a diverse group of integral membrane proteins that are involved in many essential cellular processes, including signal transduction, cell adhesion, and transmembrane transport of materials. Dysregulation of the SPTMRs is linked with many human diseases. Despite extensive efforts in past decades, the mechanisms of action of the SPTMRs remain incompletely understood. One major hurdle is the lack of structures of the full-length SPTMRs in different functional states. Such structural information is difficult to obtain by traditional structural biology methods such as X-ray crystallography and nuclear magnetic resonance (NMR). The recent rapid development of single-particle cryo-electron microscopy (cryo-EM) has led to an exponential surge in the number of high-resolution structures of integral membrane proteins, including SPTMRs. Cryo-EM structures of SPTMRs solved in the past few years have tremendously improved our understanding of how SPTMRs function. In this review, we will highlight these progresses in the structural studies of SPTMRs by single-particle cryo-EM, analyze important structural details of each protein involved, and discuss their implications on the underlying mechanisms. Finally, we also briefly discuss remaining challenges and exciting opportunities in the field.

中文翻译：

单程跨膜受体的冷冻电子显微镜分析

单次跨膜受体 (SPTMR) 代表一组不同的整合膜蛋白，它们参与许多重要的细胞过程，包括信号转导、细胞粘附和物质的跨膜转运。SPTMRs 的失调与许多人类疾病有关。尽管在过去几十年中做出了广泛的努力，但 SPTMR 的作用机制仍未完全了解。一个主要障碍是缺乏不同功能状态下的全长 SPTMR 结构。这种结构信息很难通过X射线晶体学和核磁共振（NMR）等传统结构生物学方法获得。最近单粒子冷冻电子显微镜 (cryo-EM) 的快速发展导致完整膜蛋白（包括 SPTMR）的高分辨率结构数量呈指数级增长。过去几年解决的 SPTMR 冷冻电镜结构极大地提高了我们对 SPTMR 功能的理解。在这篇综述中，我们将重点介绍通过单粒子冷冻电子显微镜对 SPTMR 进行结构研究的这些进展，分析所涉及的每种蛋白质的重要结构细节，并讨论它们对潜在机制的影响。最后，我们还简要讨论了该领域剩余的挑战和激动人心的机遇。我们将通过单粒子冷冻电子显微镜强调 SPTMR 结构研究的这些进展，分析所涉及的每种蛋白质的重要结构细节，并讨论它们对潜在机制的影响。最后，我们还简要讨论了该领域剩余的挑战和激动人心的机遇。我们将通过单粒子冷冻电子显微镜强调 SPTMR 结构研究的这些进展，分析所涉及的每种蛋白质的重要结构细节，并讨论它们对潜在机制的影响。最后，我们还简要讨论了该领域剩余的挑战和激动人心的机遇。

更新日期：2022-06-17

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