Benning Friederike M C, Jenni Simon, Garcia Coby Y, Nguyen Tran H, Zhang Xuewu, Chao Luke H
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Department of Genetics, Harvard Medical School, Boston, MA, USA.
bioRxiv. 2023 Nov 7:2023.06.15.545104. doi: 10.1101/2023.06.15.545104.
Baculoviruses are insect-infecting pathogens with wide applications as biological pesticides, protein production vehicles and gene therapy tools. Its cylindrical nucleocapsid, which encapsulates and protects the circular double-stranded viral DNA encoding proteins for viral replication and entry, is formed by the highly conserved major capsid protein VP39. The mechanism for VP39 assembly remains unknown. We determined a 3.2 Å electron cryomicroscopy helical reconstruction of an infectious nucleocapsid of multiple nucleopolyhedrovirus, revealing how dimers of VP39 assemble into a 14-stranded helical tube. We show that VP39 comprises a unique protein fold conserved across baculoviruses, which includes a Zinc finger domain and a stabilizing intra-dimer sling. Analysis of sample polymorphism revealed that VP39 assembles in several closely-related helical geometries. This VP39 reconstruction reveals general principles for baculoviral nucleocapsid assembly.
杆状病毒是感染昆虫的病原体,作为生物杀虫剂、蛋白质生产载体和基因治疗工具具有广泛应用。其圆柱形核衣壳由高度保守的主要衣壳蛋白VP39形成,该核衣壳包裹并保护编码用于病毒复制和进入的蛋白质的环状双链病毒DNA。VP39组装的机制仍然未知。我们确定了多角体核型多角体病毒感染性核衣壳的3.2埃电子冷冻显微镜螺旋重建,揭示了VP39二聚体如何组装成14链螺旋管。我们表明,VP39包含一种在杆状病毒中保守的独特蛋白质折叠,其中包括一个锌指结构域和一个稳定的二聚体内吊带。对样品多态性的分析表明,VP39以几种密切相关的螺旋几何结构组装。这种VP39重建揭示了杆状病毒核衣壳组装的一般原则。