Cantini Francesca, Savino Silvana, Scarselli Maria, Masignani Vega, Pizza Mariagrazia, Romagnoli Giacomo, Swennen Erwin, Veggi Daniele, Banci Lucia, Rappuoli Rino
Centro Risonanze Magnetiche (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
J Biol Chem. 2006 Mar 17;281(11):7220-7. doi: 10.1074/jbc.M508595200. Epub 2005 Dec 31.
GNA1870, a 28-kDa surface-exposed lipoprotein of Neisseria meningitidis recently discovered by reverse vaccinology, is one of the most potent antigens of Meningococcus and a promising candidate for a universal vaccine against a devastating disease. Previous studies of epitope mapping and genetic characterization identified residues critical for bactericidal response within the C-terminal domain of the molecule. To elucidate the conformation of protective epitopes, we used NMR spectroscopy to obtain the solution structure of the immunodominant 18-kDa C-terminal portion of GNA1870. The structure consists of an eight-stranded antiparallel beta-barrel overlaid by a short alpha-helix with an unstructured N-terminal end. Residues previously shown to be important for antibody recognition were mapped on loops facing the same ridge of the molecule. The sequence similarity of GNA1870 with members of the bacterial transferrin receptor family allows one to predict the folding of this class of well known bacterial antigens, providing the basis for the rational engineering of high affinity B cell epitopes.
GNA1870是一种28 kDa的表面暴露脂蛋白，最近通过反向疫苗学在脑膜炎奈瑟菌中发现。它是脑膜炎球菌最有效的抗原之一，也是一种针对这种毁灭性疾病的通用疫苗的有前景的候选物。先前的表位作图和遗传特征研究确定了该分子C末端结构域内对杀菌反应至关重要的残基。为了阐明保护性表位的构象，我们使用核磁共振光谱法获得了GNA1870免疫显性18 kDa C末端部分的溶液结构。该结构由一个八链反平行β桶组成，上面覆盖着一个短的α螺旋，N末端无结构。先前显示对抗体识别重要的残基被定位在分子同一脊的环上。GNA1870与细菌转铁蛋白受体家族成员的序列相似性使人们能够预测这类著名细菌抗原的折叠，为高亲和力B细胞表位的合理工程设计提供了基础。
