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Updated: Mar 24, 2026

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging

Published on: December 1, 2011

一种原生,完全糖化,切割的HIV-1包膜剪切剂的冷EM结构

Jeong Hyun Lee¹, Gabriel Ozorowski¹, Andrew B Ward¹

¹Department of Integrative Structural and Computational Biology, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, International AIDS Vaccine Initiative Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.

Science (New York, N.Y.)

|March 5, 2016

概括

研究人员使用冷EM可视化了HIV-1包膜糖蛋白剪切剂 (Env). 这些由抗体稳定的结构提供了对原生Env构造和潜在治疗点的新见解.

科学领域:

结构生物学
病毒学
免疫学

背景情况:

艾滋病毒-1包膜糖蛋白三分剂 (Env) 通过与CD4 ((+) T细胞相互作用来调解病毒的进入.
在病毒进入过程中,Env会发生显著的形状变化,使结构研究复杂化.
之前的可溶性Envtrimers缺少关键区域,例如膜近接外部区域 (MPER).

研究的目的:

通过冷电子显微镜 (cryo-EM) 确定稳定HIV-1 Env的结构.
通过针对不同区域的广泛中和抗体来研究Env结构.

主要方法:

使用冷电子显微镜 (cryo-EM) 确定了B类HIV-1Env的结构.
通过广泛中和的抗体PGT151稳定了Env.
产生了与PGT151复合的Env重建和针对MPER的10E8抗体.

主要成果:

仅缺少细胞质尾部并被PGT151稳定的一种B类HIV-1Env的4. 2安格斯特罗姆分辨率冷EM结构得到了.
使用PGT151和10E8复合的Env实现了8.8安格斯特罗姆分辨率的重建.
这些结构为野生型HIV-1 Env结构提供了新的见解.

结论:

呈现的冷EM结构提供了前所未有的HIV-1 Env trimer在近乎原生状态的视图.
使用像PGT151这样的抗体进行稳定,并包括针对MPER的抗体,以方便其结构的确定.
这些发现有助于我们更好地了解HIV-1的进入机制和抗体相互作用,并为疫苗设计提供了信息.

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相关概念视频

Cryo-electron Microscopy

Cryo-electron Microscopy

Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...