3V6F

Crystal Structure of an anti-HBV e-antigen monoclonal Fab fragment (e6), unbound

Summary for 3V6F

• Entry DOI: 10.2210/pdb3v6f/pdb
• Related: 3V6Z
• Descriptor: Fab e6 Heavy Chain, Fab e6 Light Chain (3 entities in total)
• Functional Keywords: immunoglobulin domain, antibody fab fragment, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 8
• Total formula weight: 192381.34

Authors

Dimattia, M.A.,Watts, N.R.,Stahl, S.J.,Grimes, J.M.,Steven, A.C.,Stuart, D.I.,Wingfield, P.T. (deposition date: 2011-12-19, release date: 2013-02-06, Last modification date: 2024-10-09)

Primary citation

Dimattia, M.A.,Watts, N.R.,Stahl, S.J.,Grimes, J.M.,Steven, A.C.,Stuart, D.I.,Wingfield, P.T.
Antigenic switching of hepatitis B virus by alternative dimerization of the capsid protein.
Structure, 21:133-142, 2013

PubMed Abstract: Chronic hepatitis B virus (HBV) infection afflicts millions worldwide with cirrhosis and liver cancer. HBV e-antigen (HBeAg), a clinical marker for disease severity, is a nonparticulate variant of the protein (core antigen, HBcAg) that forms the building-blocks of capsids. HBeAg is not required for virion production, but is implicated in establishing immune tolerance and chronic infection. Here, we report the crystal structure of HBeAg, which clarifies how the short N-terminal propeptide of HBeAg induces a radically altered mode of dimerization relative to HBcAg (∼140° rotation), locked into place through formation of intramolecular disulfide bridges. This structural switch precludes capsid assembly and engenders a distinct antigenic repertoire, explaining why the two antigens are cross-reactive at the T cell level (through sequence identity) but not at the B cell level (through conformation). The structure offers insight into how HBeAg may establish immune tolerance for HBcAg while evading its robust immunogenicity.

PubMed: 23219881
DOI: 10.1016/j.str.2012.10.017

Experimental method

X-RAY DIFFRACTION (2.52 Å)