Structural polymorphism of the major capsid protein of rotavirus.
Rotaviruses are important human pathogens with a triple-layered icosahedral capsid. The major capsid protein VP6 is shown here to self-assemble into spherical or helical particles mainly depending upon pH. Assembly is inhibited either by low pH (<3.0) or by a high concentration (>100 mM) of divalent cations (Ca(2+) and Zn(2+)). The structures of two types of helical tubes were determined by electron cryomicroscopy and image analysis to a resolution of 2.0 and 2.5 nm. In both reconstructions, the molecular envelope of VP6 fits the atomic model determined by X-ray crystallography remarkably well. The 3-fold symmetry of the VP6 trimer, being incompatible with the helical symmetry, is broken at the level of the trimer contacts. One type of contact is maintained within all VP6 particles (tubes and virus), strongly suggesting that VP6 assemblies arise from different packings of a unique dimer of trimers. Our data show that the protonation state and thus the charge distribution are important switches governing the assembly of macromolecular assemblies.
Lepault
J
J
Laboratoire de Génétique des Virus, CNRS-UPR 9053 1, Avenue de la Terrasse Bâtiment 14C, F-91198 Gif-sur-Yvette Cedex, France. lepault@gv.cnrs-gif.fr
Petitpas
I
I
Erk
I
I
Navaza
J
J
Bigot
D
D
Dona
M
M
Vachette
P
P
Cohen
J
J
Rey
F A
FA
D000956:Antigens, Viral; D002213:Capsid / Q000737:chemistry* / Q000648:ultrastructure; D036022:Capsid Proteins; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000648:ultrastructure; D012401:Rotavirus / Q000737:chemistry* / Q000648:ultrastructure
D000956:Antigens, Viral; D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; C061332:VP6 protein, Rotavirus