Kinetically coupled folding of a single HIV-1 glycoprotein 41 complex in viral membrane fusion and inhibition
文献类型：期刊论文
| 作者 | Jiao, JY; Rebane, AA; Ma, L; Gao, Y; Zhang, YL |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2015 |
| 卷号 | 112期号:22页码:E2855-E2864 |
| 关键词 | gp41 complex optical tweezers protein folding fusion inhibitor viral fusion |
| 通讯作者 | Zhang, YL (reprint author), Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06511 USA.,yongli.zhang@yale.edu |
| 英文摘要 | HIV-1 glycoprotein 41 (gp41) mediates viral entry into host cells by coupling its folding energy to membrane fusion. Gp41 folding is blocked by fusion inhibitors, including the commercial drug T20, to treat HIV/AIDS. However, gp41 folding intermediates, energy, and kinetics are poorly understood. Here, we identified the folding intermediates of a single gp41 trimer-of-hairpins and measured their associated energy and kinetics using high-resolution optical tweezers. We found that folding of gp41 hairpins was energetically independent but kinetically coupled: Each hairpin contributed a folding energy of similar to-23 k(B)T, but folding of one hairpin successively accelerated the folding rate of the next one by similar to 20-fold. Membrane-mimicking micelles slowed down gp41 folding and reduced the stability of the six-helix bundle. However, the stability was restored by cooperative folding of the membrane-proximal external region. Surprisingly, T20 strongly inhibited gp41 folding by actively displacing the C-terminal hairpin strand in a force-dependent manner. The inhibition was abolished by a T20-resistant gp41 mutation. The energetics and kinetics of gp41 folding established by us provides a basis to understand viral membrane fusion, infection, and therapeutic intervention. |
| 学科主题 | Science & Technology - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 关键词[WOS] | IMMUNODEFICIENCY-VIRUS TYPE-1 ; RESOLUTION OPTICAL TWEEZERS ; ENVELOPE GLYCOPROTEIN ; COILED-COIL ; PROXIMAL REGION ; GP41 ECTODOMAIN ; PROTEIN ; MOLECULE ; SNARE ; ENTRY |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000355832200006 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/100]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Jiao, JY,Rebane, AA,Ma, L,et al. Kinetically coupled folding of a single HIV-1 glycoprotein 41 complex in viral membrane fusion and inhibition[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2015,112(22):E2855-E2864. |
| APA | Jiao, JY,Rebane, AA,Ma, L,Gao, Y,&Zhang, YL.(2015).Kinetically coupled folding of a single HIV-1 glycoprotein 41 complex in viral membrane fusion and inhibition.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,112(22),E2855-E2864. |
| MLA | Jiao, JY,et al."Kinetically coupled folding of a single HIV-1 glycoprotein 41 complex in viral membrane fusion and inhibition".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112.22(2015):E2855-E2864. |
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