title: Infectious bursal disease virus capsid assembly and maturation by structural rearrangements of a transient molecular switch.
abstract: Infectious bursal disease virus (IBDV), a double-stranded RNA (dsRNA) virus belonging to the Birnaviridae family, is an economically important avian pathogen. The IBDV capsid is based on a single-shelled T=13 lattice, and the only structural subunits are VP2 trimers. During capsid assembly, VP2 is synthesized as a protein precursor, called pVP2, whose 71-residue C-terminal end is proteolytically processed. The conformational flexibility of pVP2 is due to an amphipathic alpha-helix located at its C-terminal end. VP3, the other IBDV major structural protein that accomplishes numerous roles during the viral cycle, acts as a scaffolding protein required for assembly control. Here we address the molecular mechanism that defines the multimeric state of the capsid protein as hexamers or pentamers. We used a combination of three-dimensional cryo-electron microscopy maps at or close to subnanometer resolution with atomic models. Our studies suggest that the key polypeptide element, the C-terminal amphipathic alpha-helix, which acts as a transient conformational switch, is bound to the flexible VP2 C-terminal end. In addition, capsid protein oligomerization is also controlled by the progressive trimming of its C-terminal domain. The coordination of these molecular events correlates viral capsid assembly with different conformations of the amphipathic alpha-helix in the precursor capsid, as a five-alpha-helix bundle at the pentamers or an open star-like conformation at the hexamers. These results, reminiscent of the assembly pathway of positive single-stranded RNA viruses, such as nodavirus and tetravirus, add new insights into the evolutionary relationships of dsRNA viruses.
authors: Departamento de Estructura de Macromoléculas, Centro Nacional de Biotecnología/CSIC, C/ Darwin no. 3, Cantoblanco, E-28049 Madrid, Spain.
authors: Daniel
authors: D
authors: Luque
authors: Irene
authors: I
authors: Saugar
authors: José F
authors: JF
authors: Rodríguez
authors: Nuria
authors: N
authors: Verdaguer
authors: Damiá
authors: D
authors: Garriga
authors: Carmen San
authors: CS
authors: Martín
authors: Javier A
authors: JA
authors: Velázquez-Muriel
authors: Benes L
authors: BL
authors: Trus
authors: José L
authors: JL
authors: Carrascosa
authors: José R
authors: JR
authors: Castón
mesh_terms: D002213:Capsid / Q000737:chemistry* / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D007243:Infectious bursal disease virus / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D030381:Nodaviridae / Q000737:chemistry / Q000648:ultrastructure; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015678:Viral Structural Proteins / Q000737:chemistry* / Q000378:metabolism; D019065:Virus Assembly
chemical_list: C082513:VP2 protein, infectious bursal disease virus; D015678:Viral Structural Proteins