Infectious bursal disease virus capsid assembly and maturation by structural rearrangements of a transient molecular switch.
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.
Luque
Daniel
D
Departamento de Estructura de Macromoléculas, Centro Nacional de Biotecnología/CSIC, C/ Darwin no. 3, Cantoblanco, E-28049 Madrid, Spain.
Saugar
Irene
I
Rodríguez
José F
JF
Verdaguer
Nuria
N
Garriga
Damiá
D
Martín
Carmen San
CS
Velázquez-Muriel
Javier A
JA
Trus
Benes L
BL
Carrascosa
José L
JL
Castón
José R
JR
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
C082513:VP2 protein, infectious bursal disease virus; D015678:Viral Structural Proteins