Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain.

Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain.
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DOI:
10.1016/j.chom.2010.03.005
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发表时间:
2010-04-22
影响因子:
30.3
通讯作者:
Weissenhorn W
Weissenhorn W
中科院分区:
医学1区
文献类型:
--
作者:
Hinz A;Miguet N;Natrajan G;Usami Y;Yamanaka H;Renesto P;Hartlieb B;McCarthy AA;Simorre JP;Göttlinger H;Weissenhorn W

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限制性因子Bst 2/tetherin含有两个膜锚,其用于在不存在病毒编码的拮抗剂的情况下将包括HIV-1的一些包膜病毒保留在质膜上。这里呈现的细胞外核心的2.77 μ m晶体结构揭示了一个平行的90 μ m长的二硫键连接的卷曲螺旋结构域,而完整的细胞外结构域基于小角X射线散射数据形成了一个延伸的170 μ m长的棒状结构。突变分析表明,卷曲螺旋和N-末端区域都需要保留HIV-1,这表明细长的结构可以作为分子标尺来桥接长距离。该结构揭示了整个卷曲螺旋的大量不规则性和不稳定性,这有助于其在不存在二硫键的情况下的低稳定性。我们建议,不规则的卷曲螺旋提供构象的灵活性,并确保Bst 2/栓蛋白锚定在血浆和新形成的病毒膜不干扰出芽。
The restriction factor Bst2/tetherin contains two membrane anchors which are employed to retain some enveloped viruses including HIV-1 tethered to the plasma membrane in the absence of virus encoded antagonists. The 2.77 Å crystal structure of the extracellular core presented here reveals a parallel 90 Å long disulfide linked coiled-coil domain while the complete extracellular domain forms an extended 170 Å long rod-like structure based on small angle X-ray scattering data. Mutagenesis analyses indicate that both the coiled-coil and the N-terminal region are required for retention of HIV-1, suggesting that the elongated structure can function as a molecular ruler to bridge long distances. The structure reveals substantial irregularities and instabilities throughout the coiled-coil, which contribute to its low stability in the absence of disulfide bonds. We propose that the irregular coiled-coil provides conformational flexibility and ensures that Bst2/tetherin anchoring in the plasma and the newly formed virus membrane do not interfere with budding.
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