Molecular architecture of native HIV-1 gp120 trimers.
Molecular architecture of native HIV-1 gp120 trimers.
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DOI：
10.1038/nature07159
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发表时间：
2008-09-04
期刊：
影响因子：
64.8
通讯作者：
Subramaniam, Sriram
中科院分区：
文献类型：
--
作者：
Liu, Jun;Bartesaghi, Alberto;Borgnia, Mario J.;Sapiro, Guillermo;Subramaniam, Sriram
人和猴免疫缺陷病毒（分别为HIV和SIV）的包膜糖蛋白（Env）介导病毒与靶细胞上的细胞表面受体CD 4结合以引发感染。Env是跨膜糖蛋白（gp 41）和表面糖蛋白（gp 120）的异源二聚体，并在病毒膜表面形成三聚体。使用冷冻电子断层扫描结合三维图像分类和平均，我们报告的三维结构的三聚体Env显示在原生HIV-1的未配体状态，在复合物与广泛中和抗体b12和在三元复合物与CD 4和17 b抗体。通过拟合已知的晶体结构的单体gp 120核心的b12-和CD 4/17 b-结合的构象到密度图由电子断层扫描，我们推导出分子模型的原生HIV-1 gp 120三聚体在unliganded和CD 4-结合状态。我们证明，CD 4结合的结果在一个重大的重组的Env三聚体，导致向外旋转和位移的每个gp 120单体。这似乎与gp 41区域沿着三聚体中轴的重排相结合，导致病毒和靶细胞膜之间更紧密的接触。我们的研究结果阐明了三聚体HIV-1 gp 120相关的抗体中和和附着到靶细胞的结构和构象变化。
The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. Env is a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120), and forms trimers on the surface of the viral membrane. Using cryo-electron tomography combined with three-dimensional image classification and averaging, we report the three-dimensional structures of trimeric Env displayed on native HIV-1 in the unliganded state, in complex with the broadly neutralizing antibody b12 and in a ternary complex with CD4 and the 17b antibody. By fitting the known crystal structures of the monomeric gp120 core in the b12- and CD4/17b-bound conformations into the density maps derived by electron tomography, we derive molecular models for the native HIV-1 gp120 trimer in unliganded and CD4-bound states. We demonstrate that CD4 binding results in a major reorganization of the Env trimer, causing an outward rotation and displacement of each gp120 monomer. This appears to be coupled with a rearrangement of the gp41 region along the central axis of the trimer, leading to closer contact between the viral and target cell membranes. Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells.
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DOI：
10.1084/jem.172.4.1233
发表时间：
1990-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Healey D;Dianda L;Moore JP;McDougal JS;Moore MJ;Estess P;Buck D;Kwong PD;Beverley PC;Sattentau QJ
通讯作者：
Sattentau QJ
影响因子：
4.8
作者：
Bennett, Adam;Liu, Jun;Subramaniam, Sriram
通讯作者：
Subramaniam, Sriram
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
64.8
作者：
Wyatt, R;Kwong, PD;Sodroski, JG
通讯作者：
Sodroski, JG
影响因子：
5.4
作者：
Johnson, WE;Morgan, J;Desrosiers, RC
通讯作者：
Desrosiers, RC