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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Single-particle cryoelectron microscopy analysis reveals the HIV-1 spike as a tripod structure
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Single-particle cryoelectron microscopy analysis reveals the HIV-1 spike as a tripod structure

机译：单粒子冷冻电子显微镜分析显示HIV-1尖峰为三脚架结构

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摘要

The HIV-1 spike is a trimer of the transmembrane gp41 and the per ipheral gp120 subunit pair. It is activated for virus-cell membrane fusion by binding sequentially to CD4 and to a chemokine receptor. Here we have studied the structural transition of the trimeric spike during the activation process. We solubilized and isolated unliganded and CD4-bound spikes from virus-like particles and used cryoelectron microscopy to reconstruct their 3D structures. In order to increase the yield and stability of the spike, we used an endodomain deleted and gp120-gp41 disulfide-linked variant. The unliganded spike displayed a hollow cage-like structure where the gp120-gp41 protomeric units formed a roof and bottom, and separated lobes and legs on the sides. The tripod structure was ver ified by fitting the recent atomic core structure of gp120 with intact N- and C-terminal ends into the spike density map. This defined the lobe as gp120 core, showed that the legs contained the polypep tide termini, and suggested the deleted variable loops V1/V2 and V3 to occupy the roof and gp41 the bottom. CD4 binding shifted the roof density peripherally and condensed the bottom density centrally. Fitting with a V3 containing gp120 core suggested that the V1/V2 loops in the roof were displaced laterally and the V3 lifted up, while the core and leg were kept in place. The loop dis placements probably prepared the spike for coreceptor interaction and roof opening so that a new fusion-active gp41 structure, assembled at the center of the cage bottom, could reach the target membrane.
机译：HIV-1尖峰是跨膜gp41和周围gp120亚基对的三聚体。通过依次结合CD4和趋化因子受体，将其激活以用于病毒-细胞膜融合。在这里，我们研究了三聚体峰在激活过程中的结构转变。我们从病毒样颗粒中溶解并分离了未配体和CD4结合的尖峰，并使用冷冻电子显微镜重建了它们的3D结构。为了提高穗的产量和稳定性，我们使用了内域缺失和gp120-gp41二硫键连接的变体。未配体的长钉显示出空心的笼状结构，其中gp120-gp41的原型单元形成了顶部和底部，并在侧面分开了裂片和腿。通过将具有完整N端和C端的gp120的最新原子核结构拟合到尖峰密度图中，可以验证三脚架结构。这将叶片定义为gp120核心，表明支腿包含息肉末端，并建议删除变量循环V1 / V2和V3占据屋顶，而gp41占据底部。 CD4的结合使屋顶密度向四周移动，并使底部密度在中央冷凝。装有包含gp120核心的V3的建议表明，车顶中的V1 / V2环向侧面移动，V3抬起，同时核心和支腿保持在原位。环状移位可能为共受体相互作用和屋顶打开准备了尖峰，以便组装在笼底中央的新型融合活性gp41结构可以到达目标膜。

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