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【medical-news】研究发现HIV多肽进入细胞的可能通
1/17/2008
研究发现HIV多肽进入细胞的可能通路
Source: Rensselaer Polytechnic Institute
来源：Rensselaer Polytechnic研究所
Troy, N.Y. - Two theoretical physicists at Rensselaer Polytechnic Institute have uncovered what they believe is the long-sought-after pathway that an HIV peptide takes to enter healthy cells. The theorists analyzed two years of biocomputation and simulation to uncover a surprisingly simple mechanism describing how this protein fragment penetrates the cell membrane. The discovery could help scientists treat other human illnesses by exploiting the same molecules that make HIV so deadly proficient.
Rensselaer Polytechnic研究所的两个理论物理学家认为他们发现了他们长期追寻的HIV多肽进入健康细胞的途径。这两个理论学家用了2年的时间进行生物学计算和模拟，发现了一个惊人的简单机制，蛋白片段正式在这种机制下穿透了细胞膜。借助对相同分子的探索，这个发现能够帮助科学家治疗其它人类疾病。
The findings are detailed in the Dec. 26, 2007, issue of the Proceedings of the National Academy of Sciences (PNAS).
该发现被刊登在2007年12月26日的美国科学院院刊上。
For the last decade, scientists have known that a positively charged, 11-amino-acid chain of HIV (HIV-1 Tat protein) can do the nearly unthinkable ¡X cross through the cell membrane. Sometimes referred to as an "arrow protein," HIV-1 Tat pierces the cell membrane and carries a cargo through the cell membrane.
最近10年，科学家们发现，HIV-1的tat蛋白，一个带正电的11个氨基酸组成的肽链，能够完成机会是不可能的细胞膜穿越。有时候将HIV tat蛋白称作“箭头”蛋白，它能够刺穿细胞膜然后携带“货物”通过细胞膜。
Its unique cell-puncturing ability has been the subject of hundreds of scientific articles investigating the type of materials that can piggyback on the peptide and also enter the cell. Researchers have proposed using the peptide to deliver genes for gene therapy and drugs that need to be delivered directly to a cell. But despite many potential medical applications, the actual mechanism that opens the holes in the cell remained undiscovered.
Tat蛋白独一无二的细胞穿透能力使它成为上百篇科学论文的主题，主要集中在何种类型的物质能够通过该多肽转运而进入细胞。研究者提出用这个多肽转运基因用于基因治疗，转运药物来对细胞进行直接靶向性治疗。尽管有许多潜在性的医学应用，但tat蛋白如何在细胞上“打洞”的真正机制尚不清楚。
The Rensselaer researchers have discovered that the positively charged HIV peptide is drawn to negatively charged groups inside the cell membrane. When the HIV peptide cannot satisfy itself with the negative charges available on the cell membrane surface it is directly attached to, it reaches through the membrane to grab negatively charged groups in the molecules on the other side, opening a transient hole in the cell.
Rensselaer的研究者发现，细胞膜内部带负电的基团吸引HIV带正电的多肽。当HIV多肽直接与细胞膜结合但细胞膜表面的负电荷不能满足其需要，它便在细胞表面开一个暂时的洞，穿过细胞膜与另一边的负电分子基团结合。
"What we saw in our computer calculations wasn't at all what we expected to see when we began," said co-lead author and Senior Constellation Professor of Biocomputation and Bioinformatics Angel Garcia. "The mechanism for entrance in the cell was clear in one simulation, but in some instances simulations show one result and you never see that result again. Then we started doing other simulations and it kept happening again and again."
该研究的共同领衔作者，生物计算机和生物信息学的著名教授Angel Garcia说：“开始我们在计算机上计算的结果与我们的想像完全不一致，有时候在一种模拟的情况下，进入细胞的机制很清楚，但这种结果有时候仅仅是昙花一现，从此再也不出现。然后，我们开始作其它模拟，并获得良好的重复性。”
Garcia and his collaborator, postdoctoral researcher Henry Herce, initially set out to uncover how the peptide interacts with a lipid bilayer that is used to model the cell membrane. A highly efficient biological system, the cell membrane is composed of a lipid bilayer (made up of two monolayers) designed to protect the cell by preventing the influx of material. Each lipid in the bilayer has a polar, or charged, end and a non-polar end. A monolayer of lipids faces the exterior of the cell, with the polar end facing the outside of the cell. Another monolayer is under the first layer, forming the bilayer. The polar end of the lower layer faces the interior of the cell, forming a middle section containing the uncharged halves of both monolayers.
Garcia和他的合作者博士后研究者Henry Herce第一步是揭示这个多肽与磷脂双层是如何相互作用的，磷脂双层是细胞膜的模型。细胞膜是一个有效的生物学系统，它由磷脂双层组成，防止细胞外物质内流。磷脂双层的每个磷脂都有极性或带电荷一端和非极性一端，细胞外层的磷脂单层其极性端朝向细胞外，另外一层的磷脂单层极性端朝向细胞内，中间是两个单层的不带电的非极性端。
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作者:admin@医学,生命科学 2011-05-25 05:14
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