Cryo-electron microscopy studies of empty capsids of human parvovirus B19 complexed with its cellular receptor.

The three-dimensional structures of human parvovirus B19 VP2 capsids, alone and complexed with its cellular receptor, globoside, have been determined to 26 resolution. The B19 capsid structure, reconstructed from cryo-electron micrographs of vitrified specimens, has depressions on the icosahedral 2-fold and 3-fold axes, as well as a canyon-like region around the 5-fold axes. Similar results had previously been found in an 8 angstrom resolution map derived from x-ray diffraction data. Other parvoviral structures have a cylindrical channel along the 5-fold icosahedral axes, whereas density covers the 5-fold axes in B19. The glycolipid receptor molecules bind into the depressions on the 3-fold axes of the B19:globoside complex. A model of the tetrasaccharide component of globoside, organized as a trimeric fiber, fits well into the difference density representing the globoside receptor. Escape mutations to neutralizing antibodies map onto th capsid surface at regions immediately surrounding the globoside attachment sites. The proximity of the antigenic epitopes to the receptor site suggests that neutralization of virus infectivity is caused by preventing attachment of viruses to cells. IMAGES:

人类细小病毒B19 VP2衣壳的三维结构（包括游离形式，以及与其细胞受体（cellular receptor）红细胞糖苷脂（globoside）结合的复合物形式），已解析至26分辨率。该B19衣壳结构由玻璃化标本（vitrified specimens）的冷冻电子显微图重构得到，其二十面体2次轴与3次轴处存在凹陷，5次轴周围则存在峡谷状区域。此前基于X射线衍射（x-ray diffraction）数据得到的8埃分辨率图谱中，也曾观测到类似结构特征。其他细小病毒的结构在二十面体5次轴处存在圆柱形通道，而B19的5次轴处则被电子密度覆盖。糖脂受体（glycolipid receptor）分子结合至B19-红细胞糖苷脂复合物的3次轴凹陷处。以三聚体纤维（trimeric fiber）形式排布的红细胞糖苷脂四糖（tetrasaccharide）组分模型，可很好地匹配代表该受体的差密度（difference density）图。针对中和抗体（neutralizing antibodies）的逃逸突变（escape mutations）位点，分布于衣壳表面紧邻红细胞糖苷脂结合位点的区域。抗原表位（antigenic epitopes）与受体结合位点的邻近性表明，病毒感染性的中和作用是通过阻断病毒与细胞的结合实现的。图像：