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Hepatitis B Virus Genotype G forms core-like particles with unique structural properties.

Cotelesage JJ, Osiowy C, Lawrence C, DeVarennes SL, Teow S, Beniac DR, Booth TF - J. Viral Hepat. (2011)

Bottom Line: This results in a twelve amino acid insertion at the N-terminal end of the core protein, and two stop codons in the precore region that prevent the expression of HBeAg.We show that the position of the insertion would not interfere with translocation of nucleic acids through the pores to the core interior compartment.However, the insertion may partially obscure several residues on the core surface that are known to play a role in envelopment and secretion of virions, or that could affect structural rearrangements that may trigger envelopment after DNA second-strand synthesis.

View Article: PubMed Central - PubMed

Affiliation: Viral Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.

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(a) and (b). Stereo images of the HBV/A core protein structure. The red ribbon is the HBV/A core crystal structure, PDB accession 1QGT, and the yellow density is the structure derived from the HBV/A core X-ray crystallography data displayed at 14 Å resolution, to match resolution of the difference map shown in blue. The additional mass found on HBV/G (blue density) was determined by subtracting the HBV/A structure from the HBV/G structure. (a) The mass from the extra 12 amino acids on the N-terminal end of HBV/G is near to the N-terminal end of the HBV/A core (the portion of the ribbon coloured green). (b) Top view looking down one of the spike 2-fold axes. Locations of the amino acids critical for the encapsidation of the mature HBV particle, and that interact with the cytoplasmic domains of the HBsAg, are shown as purple spheres. The extra mass from the 12 amino acid insert may stearically interfere with access to some of these residues (notably S17, F18, L60, L95). (c) Side and top views of HBV/G core protein model (red ribbon) with the12 residue N-terminal insertion (yellow ribbon) modelled into the difference map density (transparent blue). Only one copy of the core molecule within the dimer is shown for clarity.
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fig03: (a) and (b). Stereo images of the HBV/A core protein structure. The red ribbon is the HBV/A core crystal structure, PDB accession 1QGT, and the yellow density is the structure derived from the HBV/A core X-ray crystallography data displayed at 14 Å resolution, to match resolution of the difference map shown in blue. The additional mass found on HBV/G (blue density) was determined by subtracting the HBV/A structure from the HBV/G structure. (a) The mass from the extra 12 amino acids on the N-terminal end of HBV/G is near to the N-terminal end of the HBV/A core (the portion of the ribbon coloured green). (b) Top view looking down one of the spike 2-fold axes. Locations of the amino acids critical for the encapsidation of the mature HBV particle, and that interact with the cytoplasmic domains of the HBsAg, are shown as purple spheres. The extra mass from the 12 amino acid insert may stearically interfere with access to some of these residues (notably S17, F18, L60, L95). (c) Side and top views of HBV/G core protein model (red ribbon) with the12 residue N-terminal insertion (yellow ribbon) modelled into the difference map density (transparent blue). Only one copy of the core molecule within the dimer is shown for clarity.

Mentions: Superficially, the three-dimensional structure of the T = 4 capsid formed by HBV/G core protein looks very similar to the crystal structure of the HBV/A capsid, PDB accession 1QGT (Figs 2a,b) [4]. The difference map created shows additional mass around the base of the spikes of the HBV core protomers (Figs 2c,d). When the difference map is superimposed with the HBV/A atomic coordinates the additional mass of the HBV/G structure is found to be adjacent to the N-terminal residues of the core protein (Fig. 2d and Figs 3a, b). The extra mass protrudes from the surface of the core particle and sits beside the capsid pores and not over them, so this feature would not effectively reduce the diffusive movement of nucleotide triphosphates into the core interior, or affect the release of nucleic acids from the core (Fig. 3a, b). When modelling the extra 12 residues by TASSER/COOT, it was apparent that there are a number of possible arrangements that 12 residues can take up and still be contained within the corresponding density (Fig. 3c). Previously, a crystal structure of an HBV capsid protein engineered with an additional 11 residue extension to its N-terminal end has been determined, PDB accession 2QIJ [21]. Although the orientation was different from that observed in HBV/G, both additional masses were pointing away from the four-helix bundle as opposed to interacting with the main body of the core protein (Fig. 3c).


Hepatitis B Virus Genotype G forms core-like particles with unique structural properties.

Cotelesage JJ, Osiowy C, Lawrence C, DeVarennes SL, Teow S, Beniac DR, Booth TF - J. Viral Hepat. (2011)

(a) and (b). Stereo images of the HBV/A core protein structure. The red ribbon is the HBV/A core crystal structure, PDB accession 1QGT, and the yellow density is the structure derived from the HBV/A core X-ray crystallography data displayed at 14 Å resolution, to match resolution of the difference map shown in blue. The additional mass found on HBV/G (blue density) was determined by subtracting the HBV/A structure from the HBV/G structure. (a) The mass from the extra 12 amino acids on the N-terminal end of HBV/G is near to the N-terminal end of the HBV/A core (the portion of the ribbon coloured green). (b) Top view looking down one of the spike 2-fold axes. Locations of the amino acids critical for the encapsidation of the mature HBV particle, and that interact with the cytoplasmic domains of the HBsAg, are shown as purple spheres. The extra mass from the 12 amino acid insert may stearically interfere with access to some of these residues (notably S17, F18, L60, L95). (c) Side and top views of HBV/G core protein model (red ribbon) with the12 residue N-terminal insertion (yellow ribbon) modelled into the difference map density (transparent blue). Only one copy of the core molecule within the dimer is shown for clarity.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3116152&req=5

fig03: (a) and (b). Stereo images of the HBV/A core protein structure. The red ribbon is the HBV/A core crystal structure, PDB accession 1QGT, and the yellow density is the structure derived from the HBV/A core X-ray crystallography data displayed at 14 Å resolution, to match resolution of the difference map shown in blue. The additional mass found on HBV/G (blue density) was determined by subtracting the HBV/A structure from the HBV/G structure. (a) The mass from the extra 12 amino acids on the N-terminal end of HBV/G is near to the N-terminal end of the HBV/A core (the portion of the ribbon coloured green). (b) Top view looking down one of the spike 2-fold axes. Locations of the amino acids critical for the encapsidation of the mature HBV particle, and that interact with the cytoplasmic domains of the HBsAg, are shown as purple spheres. The extra mass from the 12 amino acid insert may stearically interfere with access to some of these residues (notably S17, F18, L60, L95). (c) Side and top views of HBV/G core protein model (red ribbon) with the12 residue N-terminal insertion (yellow ribbon) modelled into the difference map density (transparent blue). Only one copy of the core molecule within the dimer is shown for clarity.
Mentions: Superficially, the three-dimensional structure of the T = 4 capsid formed by HBV/G core protein looks very similar to the crystal structure of the HBV/A capsid, PDB accession 1QGT (Figs 2a,b) [4]. The difference map created shows additional mass around the base of the spikes of the HBV core protomers (Figs 2c,d). When the difference map is superimposed with the HBV/A atomic coordinates the additional mass of the HBV/G structure is found to be adjacent to the N-terminal residues of the core protein (Fig. 2d and Figs 3a, b). The extra mass protrudes from the surface of the core particle and sits beside the capsid pores and not over them, so this feature would not effectively reduce the diffusive movement of nucleotide triphosphates into the core interior, or affect the release of nucleic acids from the core (Fig. 3a, b). When modelling the extra 12 residues by TASSER/COOT, it was apparent that there are a number of possible arrangements that 12 residues can take up and still be contained within the corresponding density (Fig. 3c). Previously, a crystal structure of an HBV capsid protein engineered with an additional 11 residue extension to its N-terminal end has been determined, PDB accession 2QIJ [21]. Although the orientation was different from that observed in HBV/G, both additional masses were pointing away from the four-helix bundle as opposed to interacting with the main body of the core protein (Fig. 3c).

Bottom Line: This results in a twelve amino acid insertion at the N-terminal end of the core protein, and two stop codons in the precore region that prevent the expression of HBeAg.We show that the position of the insertion would not interfere with translocation of nucleic acids through the pores to the core interior compartment.However, the insertion may partially obscure several residues on the core surface that are known to play a role in envelopment and secretion of virions, or that could affect structural rearrangements that may trigger envelopment after DNA second-strand synthesis.

View Article: PubMed Central - PubMed

Affiliation: Viral Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.

Show MeSH
Related in: MedlinePlus