Fig. 9

Sequence conservations and their localization in the core antigen. a Sequence alignment of the C-terminus of the full length HBcAg (WT) and the linker-hexahistidine-peptide (6His). Color code indicates amino acid sequence similarity according to Taylor [84]. The C-terminal domains (CTD) are marked with I–IV. b Multiple sequence alignment of the core antigen proteins was performed with the program “T-Coffee”, and the positions in the human core protein are indicated [9]. Sequences from hepadnaviruses of different origin and diverse tolerable human HBcAg mutation variants were used (with the following sequences: NP_040997.1 heron HBV; P0C6K0.1 heron hepatitis virus; ANN02856.1 tibetan frog hepadnavirus; AKT95193.1 white sucker HBV; AEW50173.1 parrot hepatitis B virus; AAR89922.1 ross’s goose hepatitis B virus; YP_024973.1 sheldgoose hepatitis B virus; YP_031693 snow goose HBV; ADP55743.1 duck HBV; P0C6K2.1 duck hepatitis virus white Shanghai; P0C6K1.1 duck hepatitis virus strain China; P0C6J8.1 hepatitis virus duck; P0C6J7.1 hepatitis virus 2 duck; Me.un. Melopsittacus undulatus BHBV; YP_007678002.1 bat HBV; YP_009045998.1 horseshoe bat hepatitis B virus; NP_671816.1 woodchuck HBV; P06433.1 woodchuck hepatitis virus 2; P0C6J1.1 ground squirrel hepatitis; P89951.1 gibbon HBV; O71303.1 woolly monkey hepatitis virus; AAF33123.1 orangutan HBV; P12901.1 chimpanzee HBV; BAF49207 HuHBV genotype H; BAM05705 HuHBV genotype G; CCK33700.1 HuHBV genotype F; BAD91272 HuHBV genotype E; CCH63726.1 HuHBV genotype D; BAU25817.1 HuHBV genotype C; BAO96185.1 HuHBV genotype B; BAD91278 HuHBV genotype A; ADX43921.1 sequence of the generated chimeric HBcAg variants). Consensus represents a consensus sequence summary of more than 200 HBcAg sequence substitutions [9]. HBVdb represents a consensus sequence extracted from 1394 human HBcAg variants [85]. Highly conserved residues are colored in blue. The localization of amino acids which have a luminal surface exposer was highlighted in yellow boxes. The HBcAg domain structure is indicated by gray boxes according to [9, 56]. Black arrows indicate the sequence segment which is covered by the C-terminal linker-hexahistidine-peptide used for the alignment in a. c Two HBcAg dimers (PDB ID: 3J2V) oriented as in the capsid were visualized. Left, a luminal view is shown, whereas the right view show a lateral perspective (in gray the lumen of the capsid is indicated). In blue, the positions of the four highly conserved residues identify in the sequence alignment in b are highlighted. The highly conserved residues (his47 and gly111) which localize on the inner particle surface are indicated by blue arrows. The insets show an atomic surface model of each view