Capsids of hepatitis B virus e antigen with authentic C termini are stabilized by electrostatic interactions

Abstract

The hepatitis B virus e antigen, an alternative transcript of the core gene, is a secreted protein that maintains viral persistence. The physiological form has extended C termini relative to Cp(‐10)149, the construct used in many studies. To examine the role of the C termini, we expressed the constructs Cp(‐10)151 and Cp(‐10)154, which have additional arginine residues. Both constructs when treated with reductant formed capsids more efficiently than Cp(‐10)149. These capsids were also substantially more stable, as measured by thermal denaturation and resistance to urea dissociation. Mutagenesis suggests that electrostatic interactions between the additional arginine residues and glutamate residues on adjacent subunits play a role in the extra stabilization. These findings have implications for the physiological role and biotechnological potential of this protein.

Reply to: “Understanding HBcrAg components improves the interpretation of clinical HBcrAg assay results”

“…In our paper [2], we used the established clinical definition for "HBeAg-negative" cases determined by the HBeAg test not by HBeAg related proteins which could be detected by both HBcrAg assays. The difference would be illustrated by the example as the capsid-like structures consisted of HBe polypeptides carrying different ctermini [3] or not carrying di-sulfide bonding between Cys (-7) and Cys (61) or of HBe protein [4], that cannot be detected by HBeAg test however could be theoretically detected by HBcrAg assays. Therefore, clinical HBeAg-negative cases are not the same as HBerelated protein-negative cases.…”

Structural and Functional Characterizations of Cancer Targeting Nanoparticles Based on Hepatitis B Virus Capsid

“…A Fourier shell correlation (FSC) of 0.143 was chosen as the cutoff for resolution determination, and the final resolutions of HAF (T = 4 state) and HAF (T = 3 state) were 3.86 Å and 3.60 Å , respectively (Figure 3a,b). The density map of the affibody was not clearly visible since the connected linkers induced flexibility of the affibody, causing the structures of HAF to appear HBcAg, the scaffold of HAF, has a Tm of 70 • C [28]. HAF, which has a tandem repeat of affibody, is more stable to heat than HBcAg as based on Tm values.…”

The Hepatitis B Virus Envelope Proteins: Molecular Gymnastics Throughout the Viral Life Cycle

“…Abbreviations: C, core; L, large; MD, matrix domain; pgRNA, pregenomic RNA; S, small. competent to coassemble with C protein dimers into mixed heterocapsids devoid of viral replication complexes (164,(166)(167)(168)(169).…”