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标签:X射线 晶体学
摘要 : 人们最近发现了一大类具有广泛中和活性的人类抗体,它们能够强力中和全部四个登革热病毒血清型。

 人们最近发现了一大类具有广泛中和活性的人类抗体,它们能够强力中和全部四个登革热病毒血清型。这一发现让我们看到一个希望:也许有可能设计一种疫苗,来提供针对该疾病的严重形式的保护作用。Alexander Rouvinski等人报告了与登革热病毒 “包膜蛋白-E”的可溶二聚物形式形成复合物的四种这类抗体的X-射线晶体结构。这些抗体能够识别一个“四元表位”(quaternary epitope),并且表现出针对全部四个病毒子类型的强烈中和活性。


Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Dengue disease is caused by four different flavivirus1 serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype2 . Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This ‘E-dimer-dependent epitope’ is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles’ heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.

对应Nature杂志: 2015年04月02日Nature杂志精选

来源: Nature 浏览次数:1


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