Tan Ming, Fang Pingan, Chachiyo Teepanis, Xia Ming, Huang Pengwei, Fang Zhaoyin, Jiang Wen, Jiang Xi
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Virology. 2008 Dec 5;382(1):115-23. doi: 10.1016/j.virol.2008.08.047. Epub 2008 Oct 16.
Noroviruses are an important cause of epidemic acute gastroenteritis and the viruses recognize human histo-blood group antigens (HBGAs) as receptors. The protruding (P) domain of noroviral capsid, the receptor-binding domain, forms subviral particles in vitro that retain the receptor-binding function. In this study we characterized the structure and HBGA-binding function of the P particle. Structure reconstruction using cryo-EM showed that the P particles are comprised of 12 P dimers that are organized in octahedral symmetry. The dimeric packing of the proteins in the P particles is similar to that in the norovirus capsid, in which the P2 subdomain with the receptor-binding interface is located at the outermost surface of the P particle. The P particles are immunogenic and reveal similar antigenic and HBGA-binding profiles with their parental virus-like particle, further confirming the shared surface structures between the two types of particles. The P particles are easily produced in E. coli and yeast and are stable, which are potentially useful for a broad application including vaccine development against noroviruses.
诺如病毒是流行性急性肠胃炎的一个重要病因,且该病毒将人组织血型抗原(HBGAs)识别为受体。诺如病毒衣壳的突出(P)结构域即受体结合结构域,在体外形成保留受体结合功能的亚病毒颗粒。在本研究中,我们对P颗粒的结构和与HBGA的结合功能进行了表征。使用冷冻电镜进行的结构重建显示,P颗粒由12个P二聚体组成,这些二聚体呈八面体对称排列。P颗粒中蛋白质的二聚体堆积与诺如病毒衣壳中的相似,其中具有受体结合界面的P2亚结构域位于P颗粒的最外表面。P颗粒具有免疫原性,并且与其亲本病毒样颗粒显示出相似的抗原和HBGA结合谱,进一步证实了这两种颗粒之间共有的表面结构。P颗粒易于在大肠杆菌和酵母中产生且稳定,这对于包括开发抗诺如病毒疫苗在内的广泛应用具有潜在用途。