资源环境科技发展态势分析平台

Packaging of the genome into a protein capsid and its subsequent delivery into a host cell are two fundamental processes in the life cycle of a virus. Unlike double-stranded DNA viruses, which pump their genome into a preformed capsid(1-3), single-stranded RNA (ssRNA) viruses, such as bacteriophage MS2, co-assemble their capsid with the genome(4-7); however, the structural basis of this co-assembly is poorly understood. MS2 infects Escherichia coli via the host 'sex pilus' (F-pilus) 8; it was the first fully sequenced organism(9) and is a model system for studies of translational gene regulation(10,11), RNA-protein interactions(12-14), and RNA virus assembly(15-17). Its positive-sense ssRNA genome of 3,569 bases is enclosed in a capsid with one maturation protein monomer and 89 coat protein dimers arranged in a T = 3 icosahedral lattice(18,19). The maturation protein is responsible for attaching the virus to an F-pilus and delivering the viral genome into the host during infection(8), but how the genome is organized and delivered is not known. Here we describe the MS2 structure at 3.6 angstrom resolution, determined by electron-counting cryo-electron microscopy (cryoEM) and asymmetric reconstruction. We traced approximately 80% of the backbone of the viral genome, built atomic models for 16 RNA stem-loops, and identified three conserved motifs of RNA-coat protein interactions among 15 of these stem-loops with diverse sequences. The stem-loop at the 3' end of the genome interacts extensively with the maturation protein, which, with just a six-helix bundle and a six-stranded beta-sheet, forms a genome-delivery apparatus and joins 89 coat protein dimers to form a capsid. This atomic description of genome-capsid interactions in a spherical ssRNA virus provides insight into genome delivery via the host sex pilus and mechanisms underlying ssRNA-capsid co-assembly, and inspires speculation about the links between nucleoprotein complexes and the origins of viruses.