HIV-1包膜蛋白gp41胞外近膜區(qū)域的結(jié)構(gòu)研究
發(fā)布時(shí)間：2018-09-05 08:27
【摘要】：HIV-1(人類免疫缺陷病毒1型)是一種嗜T淋巴細(xì)胞的逆轉(zhuǎn)錄病毒,在全球猖獗傳播,正在以前所未有的程度威脅著人類的健康。gp41是HIV-1包膜糖蛋白的跨膜區(qū)域,在介導(dǎo)病毒與受體細(xì)胞膜的融合中起重要作用,其胞外近膜區(qū)域(MPER)包含三個(gè)中和抗體的抗原表位,對(duì)艾滋病疫苗的研究非常重要。本文用圓二色譜和核磁共振的方法研究了MPER野生型肽(aa 656-683)及L669A和L669S突變型肽在膠束溶液中的結(jié)構(gòu)和定位。在酸性條件下,三種肽都是由兩段α-螺旋構(gòu)成,呈L-型結(jié)構(gòu),中和抗體2F5的抗原表位為α-螺旋結(jié)構(gòu),4E10的抗原表位由部分α-螺旋結(jié)構(gòu)和部分不規(guī)則結(jié)構(gòu)組成；通過順磁性探針實(shí)驗(yàn)證明野生型肽全部插入到膠束內(nèi)部,L669S突變對(duì)肽的結(jié)構(gòu)以及在膠束中的定位幾乎沒有影響,而L669A突變雖然對(duì)肽的結(jié)構(gòu)影響很小,但使肽在膠束中的定位上升至膠束頭基區(qū)域。在接近生理pH值時(shí),MPER野生型和L669S突變型肽的螺旋含量相對(duì)于酸性條件下都有所減少,兩個(gè)中和抗體的抗原表位都是由α-螺旋和不規(guī)則結(jié)構(gòu)組成,整個(gè)肽鏈在膠束內(nèi)部的插入位置變淺,N-端的酸性殘基由膠束內(nèi)部翻出至水/膜界面,進(jìn)而使得中和抗體的抗原表位更加裸露：MPER-L669A在接近生理pH值時(shí)螺旋含量明顯增加,其C-端區(qū)域更深地插入到膠束的疏水核內(nèi)。三個(gè)肽在膠束中插入的深度依次為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 偽 -helix, and the antigenic epitopes of neutralizing antibody 2F5 were 偽 -helical structure and partial irregular structure. The antigenic epitopes of neutralizing antibody 2F5 were 偽 -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 偽 -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，
本文編號(hào)：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 偽 -helix, and the antigenic epitopes of neutralizing antibody 2F5 were 偽 -helical structure and partial irregular structure. The antigenic epitopes of neutralizing antibody 2F5 were 偽 -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 偽 -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，
本文編號(hào)：2223732
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