Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab.
Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab.
复制标题
DOI：
10.1126/science.1170481
复制
发表时间：
2009-06-12
期刊：
影响因子：
--
通讯作者：
Dormitzer PR
中科院分区：
文献类型：
--
作者：
Aoki ST;Settembre EC;Trask SD;Greenberg HB;Harrison SC;Dormitzer PR
轮状病毒VP7的晶体结构结合的Fab从中和单克隆抗体显示的机制，其中一个大类的中和抗体的成员抑制轮状病毒感染，表明如何退出的Ca2+离子成为一个脱壳触发器在细胞进入，并提供了“初稿”的亚基免疫原的设计。轮状病毒外层蛋白VP7是保护性抗体的主要靶标。游离Ca 2+的去除使VP7三聚体解离，将其从病毒体中释放，并在另一外层蛋白VP4中启动渗透诱导构象变化。我们报告了与中和性单克隆抗体的Fab片段结合的VP7的晶体结构。Fab在亚基间接触的外表面结合，其通过两个Ca2+位点稳定。逃脱其他抗体中和的突变表明同一区域具有大多数中和抗体的表位。单价Fab足以中和感染性。我们提出，针对VP7的中和抗体通过稳定三聚体起作用，从而抑制VP4重排的未包被触发剂。二硫键连接的三聚体是潜在的亚基免疫原。
The crystal structure of rotavirus VP7 bound with the Fab from a neutralizing monoclonal shows the mechanism by which members of a large class of neutralizing antibodies inhibit rotavirus infection, indicates how withdrawal of Ca2+ ions becomes an uncoating trigger during cell entry, and provides the “first draft” of a design for subunit immunogens. Rotavirus outer-layer protein VP7 is a principal target of protective antibodies. Removal of free Ca2+ dissociates the VP7 trimer, releases it from the virion, and initiates penetration-inducing conformational changes in the other outer-layer protein, VP4. We report the crystal structure of VP7 bound with the Fab fragment of a neutralizing monoclonal antibody. The Fab binds across the outer surface of the intersubunit contact, which is stabilized by two Ca2+ sites. Mutations that escape neutralization by other antibodies suggest that the same region bears the epitopes of most neutralizing antibodies. The monovalent Fab is sufficient to neutralize infectivity. We propose that neutralizing antibodies against VP7 act by stabilizing the trimer, thereby inhibiting the uncoating trigger for VP4 rearrangement. A disulfide-linked trimer is a potential subunit immunogen.
登录
查看更多内容
影响因子：
5.4
作者：
Li, Zongli;Baker, Matthew L.;Prasad, B. V. Venkataram
通讯作者：
Prasad, B. V. Venkataram
影响因子：
5.4
作者：
Graham, KL;Halasz, P;Coulson, BS
通讯作者：
Coulson, BS
影响因子：
5.4
作者：
Gajardo, R;Vende, P;Cohen, J
通讯作者：
Cohen, J
影响因子：
5.4
作者：
SVENSSON, L;DORMITZER, PR;GREENBERG, HB
通讯作者：
GREENBERG, HB
影响因子：
3.7
作者：
DORMITZER, PR;BOTH, GW;GREENBERG, HB
通讯作者：
GREENBERG, HB