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Abstract：
The study of virus structures has contributed to methodological advances in structural biology that are generally applicable (molecular replacement and noncrystallographic symmetry are just two of the best known examples). Moreover, structural virology has been instrumental in forging the more general concept of exploiting phase information derived from multiple structural techniques. This hybridization of structural methods, primarily electron microscopy (EM) and X-ray crystallography, but also small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) spectroscopy, is central to integrative structural biology. Here, the interplay of X-ray crystallography and EM is illustrated through the example of the structural determination of the marine lipid-containing bacteriophage PM2. Molecular replacement starting from an ~13 Å cryo-EM reconstruction, followed by cycling density averaging, phase extension and solvent flattening, gave the X-ray structure of the intact virus at 7 Å resolution This in turn served as a bridge to phase, to 2.5 Å resolution, data from twinned crystals of the major coat protein (P2), ultimately yielding a quasi-atomic model of the particle, which provided significant insights into virus evolution and viral membrane biogenesis.
摘要：
病毒结构的研究为普遍适用的结构生物学的方法学进步做出了贡献（分子替代和非晶体学对称性只是两个最著名的例子）。此外，结构病毒学有助于锻造更普遍的概念，即利用从多种结构技术中获得的相位信息。这种结构方法的杂交，主要是电子显微镜（EM）和X射线晶体学，还有小角度X射线散射（SAXS）和核磁共振（NMR）光谱，是综合结构生物学的核心。这里,通过海洋含脂质噬菌体PM2的结构测定实例说明了X射线晶体学和EM的相互作用。分子置换从~13µarcryo-EM重建开始，其次是循环密度平均，相延伸和溶剂平坦化，给出了完整病毒的X射线结构，分辨率为7，这反过来又充当了一个桥梁，到2.5μ分辨率，来自主要外壳蛋白（P2）的孪生晶体的数据，最终产生粒子的准原子模型，这为病毒进化和病毒膜生物发生提供了重要的见解。
