Structure and plasticity of the human immunodeficiency virus gp41 fusion domain in lipid micelles and bilayers
Structure and plasticity of the human immunodeficiency virus gp41 fusion domain in lipid micelles and bilayers
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DOI：
10.1529/biophysj.106.102335
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Tamm, Lukas K.
中科院分区：
文献类型：
--
作者：
Li, Yinling;Tamm, Lukas K.
一个彻底的了解包膜病毒在不断变化的脂质环境中的融合结构域的结构，有助于我们制定机制模型，他们如何可能在介导病毒进入膜融合。我们已经表达了HIV-1 gp 41的N-末端融合结构域作为一种构建体，该构建体在没有膜的情况下是水溶性的，但在其存在下也以高亲和力与脂质胶束和双层结合。我们已经解决了结构，并研究了这个域绑定到十二烷基磷酸胆碱胶束的动力学，通过同和异核磁共振光谱。融合肽从Ile（4）到Ala（14）形成稳定的疏水螺旋，但在从Ala（15）延伸到Ser（23）的中间极性区段中越来越无序和动态。当以低浓度与脂质双层结合时，HIV融合结构域也主要是α-螺旋的，如通过CD和FTIR光谱所确定的。然而，在更高的蛋白质/脂质比下，该结构域部分转化为脂质双层中的β结构。受控的脂质混合发生在支持α-螺旋而不是β-链构象的浓度下。
A thorough understanding of the structure of fusion domains of enveloped viruses in changing lipid environments helps us to formulate mechanistic models on how they might function in mediating viral entry by membrane fusion. We have expressed the N-terminal fusion domain of HIV-1 gp41 as a construct that is water-soluble in the absence of membranes, but that also binds with high affinity to lipid micelles and bilayers in their presence. We have solved the structure and studied the dynamics of this domain bound to dodecylphosphocholine micelles by homo- and heteronuclear NMR spectroscopy. The fusion peptide forms a stable hydrophobic helix from Ile(4) to Ala(14), but is increasingly more disordered and dynamic in a segment of intermediate polarity that stretches from Ala(15) to Ser(23). When bound to lipid bilayers at low concentration, the HIV fusion domain is also largely alpha-helical, as determined by CD and FTIR spectroscopy. However, at higher protein/lipid ratios, the domain is partially converted to form beta-structures in lipid bilayers. Controlled lipid mixing occurs at concentrations that support the alpha-helical, but not the beta-strand conformation.