Asymmetric reconstruction of the aquareovirus core at near-atomic resolution and mechanism of transcription initiation
Year: 2023
Type: article
Abstract: The Reoviridae family of dsRNA viruses is characterized by its members’ capacity for endogenous transcription of their multipartite genomes within proteinaceous capsids of 1 to 3 layers. These viruses share inner core particles (ICPs) that conform to icosahedral, T=2*, symmetry, but differ in two major respects: first, the presence or absence of RNA-capping turrets at each icosahedral vertex; second, the number of additional host-specific capsid layers that are often lost upon cell entry. While the role of these additional layers in host infection is generally understood, the absence of asymmetric ICP structures from turreted, multilayered reoviruses has obfuscated our understanding of how successive removal of these external layers impact the structural organization of the ICP and transcription initiation. Here, we present the 3.3 Å resolution structure of the aquareovirus (ARV) ICP, and atomic models of the capsid proteins VP3 and VP6, transcriptional enzymatic complex (TEC) subunits VP2 and VP4, and RNA-capping turret protein VP1. These structures reveal significant differences when compared to those of the coated ARV, as well as their counterparts in single-layered cytoplasmic polyhedrosis virus (CPV). Compared to the double-layered ARV virion and infectious subvirion particle structures, the ARV ICP undergoes significant capsid expansion and widening of the nucleotide processing channels in its TEC and turret. Thus, the loss of outer capsid layers may regulate transcription initiation in ARV, unlike CPV which relies solely on allosteric regulation by binding transcriptional cofactors. These results shed new light on the mechanism of transcription initiation amongst turreted, multilayered members of Reoviridae .
Source: Protein & Cell
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,448
Funders: National Science Foundation, McCarthy Family Foundation, James B. Pendleton Charitable Trust, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Division of Materials Research, National Center for Research Resources, UCLA AIDS Institute
Awards: G1395360581, G3299242641, MRI: Acquisition of a direct electron detector for the UCLA Titan electron microscope, Direct Detection Device for atomic resolution cryoEM of macromolecular complexes, West/Midwest Consortium for High-Resolution Cryo Electron Microscopy, G5918905806, High-End CryoEM Instrument for the UCLA Electron Imaging Center for Nanomachines, G7595416162, Science and Technology Center on Real-Time Functional Imaging (STROBE), G9000342382, Multidisciplinary Training in Microbial Pathogenesis, Genome structure, transcription and packaging of dsRNA viruses
OpenAlex ID: W4319166302