艾滋病治疗新曙光：揭秘病毒衣壳蛋白结构图

图为构成HIV病毒衣壳的CA蛋白六聚物

美首次绘制出艾滋病病毒衣壳蛋白结构图，为人类寻找艾滋病治疗新途径带来曙光。

《细胞》杂志6月11日网络版刊发文章称，美国科学家采用X光晶体照相术，首次精确描绘出构成人类艾滋病病毒(HIV)衣壳的CA蛋白六聚物结构图，为人类寻找艾滋病治疗新法带来了曙光。

自1981年艾滋病首次发现以来，所有的治疗药物都瞄准了艾滋病病毒生命周期的关键步骤，如利用蛋白酶抑制剂阻断蛋白分裂，从而防止病毒的产生。这些药物虽然在一定程度上能够延长患者的生命，但随着病毒抗药性的增强，其效用越来越不明显。

为此，科学家们开始寻求另外一种解决途径，希望通过阻碍病毒衣壳形成或摧毁病毒衣壳来削弱甚至杀死艾滋病病毒。但由于对HIV病毒衣壳的结构和形成机制没有更清楚的认识，科学家们一直无法找到相应的办法来达到目的。病毒衣壳是包围在病毒核酸外的一层蛋白质，由一定数量的壳粒组成。科学家们此前发现，HIV病毒衣壳是由大约250个六边形的蛋白团呈蜂窝状排列组合而成，其内包裹着病毒遗传物质。HIV病毒会绑定细胞表面受体，然后将衣壳转移到细胞的胞浆之中，从而感染人体细胞。

美国斯克里普斯研究所的马克·耶格尔教授和他在弗吉尼亚大学、犹他大学的同事一起，采用X光晶体照相术，第一次详细描述了构成HIV病毒衣壳的六边形蛋白体的高清分子结构，他们称这种六边形蛋白体为CA蛋白六聚物。研究人员发现，在CA蛋白六聚物中，六个氨基酸链的氮末端聚合在一起，形成六聚物的中心，而氨基酸链的碳末端则形成围绕中心的“软”带，起着连接相近六聚物的作用。大约250个这样的六聚物结合在一起，形成了病毒衣壳。由于起连接作用的“软”带非常柔软，所以这些衣壳的曲率并非固定不变。

通过观察，研究小组还发现了六聚物中相近CA蛋白分子的氨基酸氮末端与碳末端的连接方式，这对了解HIV病毒衣壳的稳定性具有重要意义，有助于科学家找到干涉这种连接的方法。比如设计出能够插入关键位置的小分子，来阻碍衣壳的形成，或者使衣壳处于不稳定状态。而任何能够使病毒衣壳不稳定的东西，不论是阻碍六聚物的聚集结合，还是促成病毒衣壳的损坏解体，都会起到削弱甚至杀死病毒的作用。

该研究项目由美国国立卫生研究院和乔治 E·休伊特医学研究基金资助。

A new dawn of AIDS treatment: Secret virus capsid protein structure

The photo shows constitute HIV virus capsid protein CA of six polymer

The United States and the first time to map out the structure of HIV capsid protein map of human search for new ways to bring AIDS treatment dawn.

"Cell" Journal of June 11 article published online edition that the U.S. scientists used X-ray crystal photography, for the first time accurately depict the human AIDS virus pose (HIV) capsid protein, six of the CA dimer structure for the human search for AIDS treatment has brought the dawn of the new law.

Since AIDS first discovered in 1981, all treatments are aimed at the HIV life cycle of the key steps, such as the use of protease inhibitors to block protein separation, in order to prevent the emergence of the virus. Although these drugs to some extent be able to extend the lives of patients, but with enhanced virus resistance, increasing its effectiveness was not obvious.

To this end, the scientists began to seek another solution, I hope, through the formation of virus capsid impede or destroy the virus capsid to weaken or even kill the AIDS virus. However, due to the HIV virus capsid structure and formation mechanism is not a better understanding, scientists have been unable to find appropriate ways to achieve the objectives. Virus capsid is surrounded by a layer of the virus nucleic acid outside the protein, by a certain number of tablets of the composition of the shell. Scientists have previously found, HIV virus capsid is approximately 250 hexagonal protein Mission was a combination of honeycomb-like arrangement in which the viral genetic material in the parcel. HIV virus cell surface receptor binding, and then transferred to the cell coat in the cytoplasm, which infected human cells.

Scripps Institute of the United States and his马克耶格尔Professor University of Virginia, the University of Utah colleagues used X-ray crystal photography, the first detailed description of the composition of the HIV virus capsid protein precursors of the hexagonal molecular structure of high-definition, they said hexagonal protein precursors such as CA VI protein oligomers. The researchers found that, in the CA protein oligomers of six, six N-terminal amino acid chain together to form the center of the six oligomers, and the amino acid carbon chain to form around the end of the center's "soft" belt, as a link between the similar The role of the six oligomers. About 250 such six oligomers combine to form the virus capsid. Since the connection from the role of "soft" with a very soft, so these capsid curvature is not fixed.

Through observation, research team also found that six CA protein oligomers in the similar amino acid molecules of nitrogen and carbon the end of the connection terminal, which is to understand the stability of HIV virus capsid is of great significance, will help scientists find the interference of such connections method. For example, to insert the key to the design of the location of small molecules to block the formation of capsid or capsid unstable so. And any can make the virus capsid instability, whether it is hindering the aggregation of six polymer combination, or contributed to damage to the disintegration of the virus capsid will weaken and even kill to play the role of the virus.

The research project by the U.S. National Institutes of Health and Medical Research, George E Hewitt Fund.

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