HIV-1包膜蛋白gp41胞外近膜区域的结构研究
发布时间：2018-09-05 08:27
【摘要】：HIV-1(人类免疫缺陷病毒1型)是一种嗜T淋巴细胞的逆转录病毒,在全球猖獗传播,正在以前所未有的程度威胁着人类的健康。gp41是HIV-1包膜糖蛋白的跨膜区域,在介导病毒与受体细胞膜的融合中起重要作用,其胞外近膜区域(MPER)包含三个中和抗体的抗原表位,对艾滋病疫苗的研究非常重要。本文用圆二色谱和核磁共振的方法研究了MPER野生型肽(aa 656-683)及L669A和L669S突变型肽在胶束溶液中的结构和定位。在酸性条件下,三种肽都是由两段α-螺旋构成,呈L-型结构,中和抗体2F5的抗原表位为α-螺旋结构,4E10的抗原表位由部分α-螺旋结构和部分不规则结构组成；通过顺磁性探针实验证明野生型肽全部插入到胶束内部,L669S突变对肽的结构以及在胶束中的定位几乎没有影响,而L669A突变虽然对肽的结构影响很小,但使肽在胶束中的定位上升至胶束头基区域。在接近生理pH值时,MPER野生型和L669S突变型肽的螺旋含量相对于酸性条件下都有所减少,两个中和抗体的抗原表位都是由α-螺旋和不规则结构组成,整个肽链在胶束内部的插入位置变浅,N-端的酸性残基由胶束内部翻出至水/膜界面,进而使得中和抗体的抗原表位更加裸露：MPER-L669A在接近生理pH值时螺旋含量明显增加,其C-端区域更深地插入到胶束的疏水核内。三个肽在胶束中插入的深度依次为MPER-L669A＞MPER-L669S≥MPER-WT。
[Abstract]:HIV-1 (Human Immunodeficiency virus 1) is a T-lymphocyte retrovirus that is rampant in the world and is threatening human health to an unprecedented extent. Gp41 is the transmembrane region of HIV-1 envelope glycoprotein. It plays an important role in mediating the fusion of virus and receptor cell membrane. The extracellular near-membrane (MPER) contains three antigenic epitopes of neutralizing antibodies, so it is very important to study the AIDS vaccine. The structure and localization of MPER wild-type peptides (aa 656-683) and L669A and L669S mutant peptides in micellar solution were studied by circular dichroism and nuclear magnetic resonance (NMR). Under acidic conditions, the three peptides were composed of two segments of 伪 -helix, and the antigenic epitopes of neutralizing antibody 2F5 were 伪 -helical structure and partial irregular structure. The antigenic epitopes of neutralizing antibody 2F5 were 伪 -helix structure and partial irregular structure. The results of paramagnetic probe experiments showed that all the wild type peptides inserted into the micelle had little effect on the structure and location of the peptide, while the L669A mutation had little effect on the structure of the peptide. However, the position of peptide in the micelle was elevated to the micellar cephalic region. The helical contents of wild type and L669S mutant peptides of mber decreased compared with those of acidic conditions at close to physiological pH value. The antigenic epitopes of both neutralizing antibodies were composed of 伪 -helix and irregular structures. The insertion position of the whole peptide chain in the micelle became shallower and the acidic residues of the N- terminal were extracted from the micelle to the water / membrane interface, which made the antigen epitope of neutralizing antibody more naked and the helical content of the N- terminal increased significantly when the physiological pH value was close to the antigenic epitope of neutralizing antibody. The C-terminal region is further inserted into the hydrophobic core of the micelle. The insertion depth of the three peptides in the micelle is MPER-L669A > MPER-L669S 鈮，
本文编号：2223732
[Abstract]:HIV-1 (Human Immunodeficiency virus 1) is a T-lymphocyte retrovirus that is rampant in the world and is threatening human health to an unprecedented extent. Gp41 is the transmembrane region of HIV-1 envelope glycoprotein. It plays an important role in mediating the fusion of virus and receptor cell membrane. The extracellular near-membrane (MPER) contains three antigenic epitopes of neutralizing antibodies, so it is very important to study the AIDS vaccine. The structure and localization of MPER wild-type peptides (aa 656-683) and L669A and L669S mutant peptides in micellar solution were studied by circular dichroism and nuclear magnetic resonance (NMR). Under acidic conditions, the three peptides were composed of two segments of 伪 -helix, and the antigenic epitopes of neutralizing antibody 2F5 were 伪 -helical structure and partial irregular structure. The antigenic epitopes of neutralizing antibody 2F5 were 伪 -helix structure and partial irregular structure. The results of paramagnetic probe experiments showed that all the wild type peptides inserted into the micelle had little effect on the structure and location of the peptide, while the L669A mutation had little effect on the structure of the peptide. However, the position of peptide in the micelle was elevated to the micellar cephalic region. The helical contents of wild type and L669S mutant peptides of mber decreased compared with those of acidic conditions at close to physiological pH value. The antigenic epitopes of both neutralizing antibodies were composed of 伪 -helix and irregular structures. The insertion position of the whole peptide chain in the micelle became shallower and the acidic residues of the N- terminal were extracted from the micelle to the water / membrane interface, which made the antigen epitope of neutralizing antibody more naked and the helical content of the N- terminal increased significantly when the physiological pH value was close to the antigenic epitope of neutralizing antibody. The C-terminal region is further inserted into the hydrophobic core of the micelle. The insertion depth of the three peptides in the micelle is MPER-L669A > MPER-L669S 鈮，
本文编号：2223732
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