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【进展|热点】观察多能蛋白,揭开HIV之谜

丁香园论坛

1008
<center> <strong>New Look at Multitalented Protein Sheds Light on Mysteries of HIV</strong></center>

ScienceDaily (Oct. 15, 2010) — New insights into the human immunodeficiency virus (HIV) infection process, which leads to acquired immunodeficiency syndrome (AIDS), may now be possible through a research method recently developed in part at the National Institute of Standards and Technology (NIST), where scientists have glimpsed an important protein molecule's behavior with unprecedented clarity.

<center> <img src="http://www.sciencedaily.com/images/2010/10/101014131912.jpg" /></center>
The Gag protein is central to the assembly of new HIV virus particles. (a) Folded Gag molecules (multicolored) arise in the cellular cytoplasm. (b) Gag binds the viral RNA (black wavy lines) and drags it into the forming particle. (c) Gag molecules also may create assembly sites, where (d) Gag must stretch out to pack into the growing virus. (e) Virus particles eventually bud off from the host cell. (Credit: NIST)

The HIV protein, known as Gag, plays several critical roles in the assembly of the human immunodeficiency virus in a host cell, but persistent difficulties with imaging Gag in a lab setting have stymied researchers' efforts to study how it functions.

"A better understanding of Gag's behavior might allow researchers to develop antiviral drugs that target the HIV assembly process, which remains unassailed by medical science," says Hirsh Nanda, a postdoctoral researcher at the NIST Center for Neutron Research (NCNR) and a member of the multi-institutional research team. "Our method might reveal how to inhibit new viruses as they grow."

The Gag molecule is a microscopic gymnast. At different stages during HIV assembly, the protein twists itself into several different shapes inside a host cell. One shape, or conformation, helps it to drag a piece of HIV genetic material toward the cell membrane, where the viral particles grow. Gag's opposite end becomes anchored there, stretching the protein into a rod-like conformation that eventually helps form a barrier surrounding the infectious genes in the finished virus. But while scientists have been aware for years that Gag appears to play several roles in HIV assembly, the specifics have remained mysterious.

The research team potentially solved this problem by creating an artificial cell membrane where Gag can show off its gymnastic prowess for the neutron probes at the NCNR. The center includes a variety of instruments specifically designed to observe large organic molecules like proteins.

"We were able to mimic the different stages of the virus's development, and look at what Gag's conformation was at these various stages," Nanda says. "We saw conformations that had never been seen before."

Nanda describes the team's first papeundefined on the subject as an important first step in describing their observational method, which was a joint effort between NIST, the National Cancer Institute and Carnegie-Mellon University. They plan another paper detailing what the method has revealed about HIV.

"Our efforts have not yet shown us how many steps are involved in Gag's work assembling an HIV particle, but at least we can see what it looks like in each major interaction that likely occurs in the cell during assembly," Nanda says. "It may allow us to characterize them for the first time."

Nanda says that their technique will also allow scientists to examine large classes of membrane proteins, which like Gag are notoriously hard to examine.

http://www.sciencedaily.com/releases/2010/10/101014131912.htm

===========================================

<center> <strong>New Look at Multitalented Protein Sheds Light on Mysteries of HIV<br /> <br /> 观察多能蛋白,揭开HIV之谜</strong><br /> <br /> 译者:Docofsoul</center>

ScienceDaily (Oct. 14, 2010) — New insights into the human immunodeficiency virus (HIV) infection process, which leads to acquired immunodeficiency syndrome (AIDS), may now be possible through a research method recently developed in part at the National Institute of Standards and Technology (NIST), where scientists have glimpsed an important protein molecule's behavior with unprecedented clarity.

《每日科学》2010年10月14日报道 ——部分由美国国家标准及技术研究所(NIST)新近开发的一种研究方法,使得科学家开始能够以前所未有的清晰度透视导致AIDS的HIV感染过程。他们所做的第一步聚焦于一种重要蛋白的活动,这种蛋白在新HIV病毒粒子的组装过程中扮演着中心角色。

<center> <img src="http://www.sciencedaily.com/images/2010/10/101014131912.jpg" /></center>

The Gag protein is central to the assembly of new HIV virus particles. (a) Folded Gag molecules (multicolored) arise in the cellular cytoplasm. (b) Gag binds the viral RNA (bl[i]ack wavy lines) and drags it into the forming particle. (c) Gag molecules also may create assembly sites, where (d) Gag must stretch out to pack into the growing virus. (e) Virus particles eventually bud off from the host cell. (Credit: NIST)

Gag蛋白在新HIV病毒粒子组装过程中扮演中心角色。(a)折叠的Gag分子(多色)在细胞质中出现;(b)Gag与病毒RNA(黑色波浪线)结合,并将其拖向正在形成的病毒粒子;(c)Gag分子也能建立组装地点,在这些地点 (d)Gag必然舒展开来、堆叠进正在生长的病毒;(e)病毒粒子最终从宿主细胞“破土而出”(照片来源:NIST)[/i]

The HIV protein, known as Gag, plays several critical roles in the assembly of the human immunodeficiency virus in a host cell, but persistent difficulties with imaging Gag in a lab setting have stymied researchers' efforts to study how it functions.

该HIV蛋白即熟知的Gag蛋白。 在宿主细胞内,Gag在人类免疫缺陷病毒的组装过程中扮演着几种至关重要的角色,但要在实验室背景下对其进行成像则遇上了反复出现的困难,妨碍了科学家对其功能发挥的具体过程的探索。

"A better understanding of Gag's behavior might allow researchers to develop antiviral drugs that target the HIV assembly process, which remains unassailed by medical science," says Hirsh Nanda, a postdoctoral researcher at the NIST Center for Neutron Research (NCNR) and a member of the multi-institutional research team. "Our method might reveal how to inhibit new viruses as they grow."

NIST中子研究中心(NIST Center for Neutron Research ,NCNR)博士后研究员、联合研究小组成员Hirsh Nanda,说:“对于Gag行为的更好理解可能允许研究者开发针对HIV组装过程的抗毒药物,而这个过程现在仍然‘逍遥法外’—— 因为目前医学对其鞭长莫及。在新病毒生长的时侯,我们的方法可能揭示对其进行抑制的具体过程。”

The Gag molecule is a microscopic gymnast. At different stages during HIV assembly, the protein twists itself into several different shapes inside a host cell. One shape, or conformation, helps it to drag a piece of HIV genetic material toward the cell membrane, where the viral particles grow. Gag's opposite end becomes anchored there, stretching the protein into a rod-like conformation that eventually helps form a barrier surrounding the infectious genes in the finished virus. But while scientists have been aware for years that Gag appears to play several roles in HIV assembly, the specifics have remained mysterious.

Gag分子是显微镜下的运动员。在HIV组装过程的不同阶段,该蛋白自行扭转,在宿主细胞内变成几种形态。其中之一的形态或构造有助于其将HIV遗传物质拖向HIV病毒粒子生长的地方——细胞膜。Gag的另一端借此下锚,将该蛋白拉长成棒状,该形态最终帮助形成围绕完工后的病毒中的感染性基因的屏障。几年来科学家已经意识到Gag可能在HIV组装过程中扮演着几种角色,但其具体过程则一直是个谜。

The research team potentially solved this problem by creating an artificial cell membrane where Gag can show off its gymnastic prowess for the neutron probes at the NCNR. The center includes a variety of instruments specifically designed to observe large organic molecules like proteins.

通过建立一种人工细胞膜使Gag能够在这个“舞台”上“一展身手”,该研究小组可能解决了这一难题。该中心包括为观察蛋白等大型有机分子而特别设计的各种工具。

"We were able to mimic the different stages of the virus's development, and look at what Gag's conformation was at these various stages," Nanda says. "We saw conformations that had never been seen before."

Nanda说:“我们能够模仿该病毒发育的不同阶段,观察不同阶段的Gag构造的具体形态。这些构造我们此前从未看到过。”

Nanda describes the team's first papeundefined on the subject as an important first step in describing their observational method, which was a joint effort between NIST, the National Cancer Institute and Carnegie-Mellon University. They plan another paper detailing what the method has revealed about HIV.

Nanda将该研究小组就这一课题所发表的首篇论文形容为其观察方法的重要的第一步。这一步是NIST、国立癌症研究院与卡内基—美隆大学的共同努力的成果。他们计划在下一篇论文中详细论述运用这一方法所揭示的有关HIV的内容。

"Our efforts have not yet shown us how many steps are involved in Gag's work assembling an HIV particle, but at least we can see what it looks like in each major interaction that likely occurs in the cell during assembly," Nanda says. "It may allow us to characterize them for the first time."

Nanda表示:“虽然目前我们所作的努力仍未能显示Gag组装HIV粒子究竟涉及多少步骤,但至少我们能够看到:在组装过程中可能出现于细胞内的每种重大的交互作用的具体过程,从而使我们得以首次能够描述其特征。”

Nanda says that their technique will also allow scientists to examine large classes of membrane proteins, which like Gag are notoriously hard to examine.

Nanda指出他们的技术也将允许科学家们检查跟Gag类似的(此前)很难检查的大种类膜蛋白。

(Docofsoul 译于2010-10-17)
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