Structure of hepatitis B surface antigen from subviral tubes determined by electron cryomicroscopy.
Hepatitis B virus consists of an icosahedral core containing the double-stranded DNA genome, enveloped by a membrane with embedded surface proteins. The crystal structure of the core protein has been solved but little information about the structure of the surface proteins has so far been available. There are three sizes of surface protein, small (S), medium (M) and large (L), which form disulfide-bonded homo- and heterodimers. The three proteins, expressed from different start sites in the coding sequence, share the common C-terminal S region; the M protein contains an additional preS2 sequence N-terminal to S, and the L protein a further preS1 sequence N-terminal to M. In infected individuals, the surface proteins are produced in huge excess over the amount needed for viral envelopment and are secreted as a heterogeneous mixture of isometric and tubular subviral particles. We have used electron cryomicroscopy to study tubular particles extracted from human serum. Helical Fourier-Bessel analysis was used to calculate a low-resolution map, although it showed that the tubes were quite disordered. From the symmetry derived from this analysis, we used single-particle methods to improve the resolution. We found that the tubes had a diameter of approximately 250 A, with spike-like features projecting from the membrane. In the plane of the membrane the proteins appear to be close packed. We propose a model for the packing arrangement of surface protein dimers in the tubes.
Medical Research Council, Cambridge, UK.
Judith M
JM
Short
Shaoxia
S
Chen
Alan M
AM
Roseman
P Jonathan G
PJ
Butler
R Anthony
RA
Crowther
D020285:Cryoelectron Microscopy; D019281:Dimerization; D006514:Hepatitis B Surface Antigens / Q000737:chemistry*; D006515:Hepatitis B virus / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D044967:Serum / Q000821:virology
D006514:Hepatitis B Surface Antigens