Membrane structure and interactions with protein and DNA in bacteriophage PRD1
Membrane structure and interactions with protein and DNA in bacteriophage PRD1
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DOI：
10.1038/nature03053
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发表时间：
2004-11-04
期刊：
影响因子：
64.8
通讯作者：
Stuart, DI
中科院分区：
文献类型：
--
作者：
Cockburn, JJB;Abrescia, NGA;Stuart, DI
膜对于选择性地控制分子进出细胞和介导细胞对其环境的反应是必不可少的。生物膜及其相关蛋白质的结构分析存在相当大的困难。尽管已经通过冷冻电子显微镜和图像重建以约9埃的分辨率对包膜病毒进行了成像（1，2），但尚未描述膜系统的详细晶体结构。通过X射线晶体学在约4埃分辨率下确定的噬菌体PRD 1颗粒的结构允许首次详细分析含膜病毒（3）。病毒衣壳的结构及其对病毒组装的影响见随附的论文（3）。在这里，我们表明，电子密度也揭示了二十面体的脂质双层，下面的蛋白质衣壳，包围病毒DNA。病毒膜含有约26，000个脂质分子，不对称地分布在膜小叶之间。内小叶主要由两性离子型磷脂酰乙醇胺分子组成，促进与病毒DNA的非常密切的相互作用，我们估计病毒DNA被包装到约45个大气压的压力，这些因素在膜介导的DNA易位到宿主细胞中期间可能是重要的。相比之下，外叶富含磷脂酰甘油和心磷脂，在二十面体不对称单元内显示出明显的侧向分离。此外，脂质头基显示出令人惊讶的有序程度。
Membranes are essential for selectively controlling the passage of molecules in and out of cells and mediating the response of cells to their environment. Biological membranes and their associated proteins present considerable difficulties for structural analysis. Although enveloped viruses have been imaged at about 9 Angstrom resolution by cryo-electron microscopy and image reconstruction(1,2), no detailed crystallographic structure of a membrane system has been described. The structure of the bacteriophage PRD1 particle, determined by X-ray crystallography at about 4 Angstrom resolution, allows the first detailed analysis of a membrane-containing virus(3). The architecture of the viral capsid and its implications for virus assembly are presented in the accompanying paper(3). Here we show that the electron density also reveals the icosahedral lipid bilayer, beneath the protein capsid, enveloping the viral DNA. The viral membrane contains about 26,000 lipid molecules asymmetrically distributed between the membrane leaflets. The inner leaflet is composed predominantly of zwitterionic phosphatidylethanolamine molecules, facilitating a very close interaction with the viral DNA, which we estimate to be packaged to a pressure of about 45 atm, factors that are likely to be important during membrane-mediated DNA translocation into the host cell. In contrast, the outer leaflet is enriched in phosphatidylglycerol and cardiolipin, which show a marked lateral segregation within the icosahedral asymmetric unit. In addition, the lipid headgroups show a surprising degree of order.