Structure of the complex of an Fab fragment of a neutralizing antibody with foot-and-mouth disease virus: Positioning of a highly mobile antigenic loop
Structure of the complex of an Fab fragment of a neutralizing antibody with foot-and-mouth disease virus: Positioning of a highly mobile antigenic loop
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DOI：
10.1093/emboj/16.7.1492
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发表时间：
1997-04-01
期刊：
影响因子：
11.4
通讯作者：
Stuart, DI
中科院分区：
文献类型：
--
作者：
Hewat, EA;Verdaguer, N;Stuart, DI
结合冷冻电子显微镜和x射线晶体学的数据，研究了口蹄疫病毒血清型C （fmdp -C）与强中和单克隆抗体（mAb） SD6的相互作用。单抗SDG与病毒蛋白1 （VP1）的长柔性gh环结合，VP1也与整合素受体结合。利用低温电子显微镜和图像分析确定了病毒- fab复合物的结构，分辨率为30埃。FMDV-C的已知结构，以及与VP1的gh -环对应的合成肽共晶的SD6 Fab的结构，都符合低温电子显微镜密度图。SD6 Fab几乎呈放射状从病毒表面投射，其方向仅与单抗的单价结合相兼容。即使考虑到单克隆抗体的铰链和肘部的灵活性，也不可能在不严重扭曲单克隆抗体的情况下模拟二价结合。结合的GN-loop本质上处于最适合Fab方向的“上”位置。SD6 Fab几乎只与VP1的gn环相互作用，与病毒衣壳的其他接触很少。与FMDV-C结合的SD6 Fab的位置和取向与先前的免疫原性数据一致。
Data from cryo-electron microscopy and X-ray crystallography have been combined to study the interactions of foot-and-mouth disease virus serotype C (FMDV-C) with a strongly neutralizing monoclonal antibody (mAb) SD6. The mAb SDG binds to the long flexible GH-loop of viral protein 1 (VP1) which also binds to an integrin receptor. The structure of the virus-Fab complex was determined to 30 Angstrom resolution using cryo-electron microscopy and image analysis. The known structure Of FMDV-C, and of the SD6 Fab co-crystallized with a synthetic peptide corresponding to the GH-loop of VP1, were fitted to the cryo-electron microscope density map. The SD6 Fab is seen to project almost radially from the viral surface in an orientation which is only compatible with monovalent binding of the mAb. Even taking into account the mAb hinge and elbow flexibility, it is not possible to model bivalent binding without severely distorting the Fabs. The bound GN-loop is essentially in what has previously been termed the 'up' position in the best fit Fab orientation. The SD6 Fab interacts almost exclusively with the GN-loop of VP1, making very few other contacts with the viral capsid. The position and orientation of the SD6 Fab bound to FMDV-C is in accord with previous immunogenic data.