title: RNA-controlled polymorphism in the in vivo assembly of 180-subunit and 120-subunit virions from a single capsid protein.
abstract: Repeated, specific interactions between capsid protein (CP) subunits direct virus capsid assembly and exemplify regulated protein-protein interactions. The results presented here reveal a striking in vivo switch in CP assembly. Using cryoelectron microscopy, three-dimensional image reconstruction, and molecular modeling, we show that brome mosaic virus (BMV) CP can assemble in vivo two remarkably distinct capsids that selectively package BMV-derived RNAs in the absence of BMV RNA replication: a 180-subunit capsid indistinguishable from virions produced in natural infections and a previously unobserved BMV capsid type with 120 subunits arranged as 60 CP dimers. Each such dimer contains two CPs in distinct, nonequivalent environments, in contrast to the quasi-equivalent CP environments throughout the 180-subunit capsid. This 120-subunit capsid utilizes most of the CP interactions of the 180-subunit capsid plus nonequivalent CP-CP interactions. Thus, the CP of BMV, and perhaps other viruses, can encode CP-CP interactions that are not apparent from mature virions and may function in assembly or disassembly. Shared structural features suggest that the 120- and 180-subunit capsids share assembly steps and that a common pentamer of CP dimers may be an important assembly intermediate. The ability of a single CP to switch between distinct capsids by means of alternate interactions also implies reduced evolutionary barriers between different capsid structures. The in vivo switch between alternate BMV capsids is controlled by the RNA packaged: a natural BMV genomic RNA was packaged in 180-subunit capsids, whereas an engineered mRNA containing only the BMV CP gene was packaged in 120-subunit capsids. RNA features can thus direct the assembly of a ribonucleoprotein complex between alternate structural pathways.
authors.affiliation: Institute for Molecular Virology, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Krol
authors.forename: N H
authors.initials: NH
authors.lastname: Olson
authors.forename: J
authors.initials: J
authors.lastname: Tate
authors.forename: J E
authors.initials: JE
authors.lastname: Johnson
authors.forename: T S
authors.initials: TS
authors.lastname: Baker
authors.forename: P
authors.initials: P
authors.lastname: Ahlquist
mesh_terms: D017795:Bromovirus / Q000502:physiology*; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D012367:RNA, Viral; D012441:Saccharomyces cerevisiae; D014771:Virion; D019065:Virus Assembly
chemical_list: D012367:RNA, Viral