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冷冻电镜技术及其应用:甾体激素受体结构。

Cryo-EM technique and its application: Structure of steroid hormone receptors.

机构信息

Department of Pharmaceutical and Biomedical Sciences, Touro College of Pharmacy, New York, NY, United States.

出版信息

Vitam Horm. 2023;123:385-397. doi: 10.1016/bs.vh.2023.02.002. Epub 2023 Mar 10.

Abstract

In recent years, cryo-electron microscopy (cryo-EM) has become one of the most powerful tools to solve the 3-D structure of macromolecules. Unlike X-ray crystallography, the cryo-EM method has advantage of providing an in-depth insight into the dynamic behavior of macromolecules, which is particularly useful to determine 3-D structural analyses of large protein complexes. Due to recent technical advancements, cryo-EM has become the method of choice for the determination of protein structures. Among other proteins, solving 3-D structure of steroid hormone receptors (SHRs) complexed with DNA and coactivators has been a challenge for decades. The limitations with X-ray crystallography and NMR to solve SHR protein structures prompted investigators to move towards cryo-EM technique. The cryo-EM structural analyses have been successful in revealing structural dynamics of several SHRs in recent years. Though, limited by low-resolution, the structural analyses of these SHRs may be useful in understanding many receptor functions as well as provide a platform to refine high-resolution structural analyses in future. This review article discusses the cryo-EM technique in general as well as structural information gained for SHRs using cryo-EM.

摘要

近年来,冷冻电子显微镜(cryo-EM)已成为解析生物大分子三维结构的最有力工具之一。与 X 射线晶体学不同,cryo-EM 方法具有深入了解生物大分子动态行为的优势,这对于确定大蛋白复合物的三维结构分析尤为有用。由于最近的技术进步,cryo-EM 已成为确定蛋白质结构的首选方法。在其他蛋白质中,解析与 DNA 和共激活因子结合的甾体激素受体(SHR)的三维结构数十年来一直是一个挑战。X 射线晶体学和 NMR 解析 SHR 蛋白结构的局限性促使研究人员转向 cryo-EM 技术。近年来,cryo-EM 结构分析成功揭示了几种 SHR 的结构动态。然而,由于分辨率较低,这些 SHR 的结构分析可能有助于理解许多受体功能,并为未来的高分辨率结构分析提供平台。本文综述了 cryo-EM 技术的一般原理,以及 cryo-EM 获得的 SHR 结构信息。

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