Structure of the meningococcal vaccine antigen NadA and epitope mapping of a bactericidal antibody
Structure of the meningococcal vaccine antigen NadA and epitope mapping of a bactericidal antibody
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DOI：
10.1073/pnas.1419686111
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发表时间：
2014-12-02
影响因子：
11.1
通讯作者：
Bottomley, Matthew James
中科院分区：
文献类型：
--
作者：
Malito, Enrico;Biancucci, Marco;Bottomley, Matthew James
B群脑膜炎奈瑟菌(MenB)是严重脓毒症和侵袭性脑膜炎球菌病的主要原因，与5-15%的死亡率和毁灭性的长期后遗症有关。NeisSerial Adherin A(NADA)是一种三聚体自身转运蛋白粘附素(TAA)，在宿主上皮细胞的黏附和侵袭中起作用，是基因组挖掘发现的三种抗原之一，属于最近被欧洲药品管理局批准的MenB疫苗的一部分。在这里，我们给出了NADA变体5在2埃分辨率下的晶体结构和疫苗中存在的NADA变体3的透射电子显微镜数据。这两个变体显示了相似的整体拓扑结构，具有新的TAA折叠，主要由三个突出的翼状结构的三聚体螺旋线圈组成，从而创建了一个不寻常的N-末端头域。用氢/氢交换质谱仪对杀菌抗体的结合部位进行了详细的定位，结果表明NADA的头部有一个保护性的构象表位。这些结果为阐明NADA的生物学功能和疫苗效力提供了重要信息。
Serogroup B Neisseria meningitidis ( MenB) is a major cause of severe sepsis and invasive meningococcal disease, which is associated with 5-15% mortality and devastating long-term sequelae. Neisserial adhesin A ( NadA), a trimeric autotransporter adhesin ( TAA) that acts in adhesion to and invasion of host epithelial cells, is one of the three antigens discovered by genome mining that are part of the MenB vaccine that recently was approved by the European Medicines Agency. Here we present the crystal structure of NadA variant 5 at 2 angstrom resolution and tranmission electron microscopy data for NadA variant 3 that is present in the vaccine. The two variants show similar overall topology with a novel TAA fold predominantly composed of trimeric coiled-coils with three protruding wing-like structures that create an unusual N-terminal head domain. Detailed mapping of the binding site of a bactericidal antibody by hydrogen/deuterium exchange MS shows that a protective conformational epitope is located in the head of NadA. These results provide information that is important for elucidating the biological function and vaccine efficacy of NadA.