Hepatitis B virus capsid: localization of the putative immunodominant loop (residues 78 to 83) on the capsid surface, and implications for the distinction between c and e-antigens.
Hepatitis B virus capsid protein comprises a 149 residue "assembly" domain that polymerizes into icosahedral particles, and a 34 residue RNA-binding "protamine" domain. Recently, the capsid structure has been studied to resolutions below 10 A by cryo-electron microscopy, revealing much of its alpha-helical substructure and that it appears to have a novel fold for a capsid protein; however, the resolution is still too low for chain-tracing by conventional criteria. Aiming to establish a fiducial marker to aid in the process of chain-tracing, we have used cryo-microscopy to pinpoint the binding site of a monoclonal antibody that recognizes the peptide from residues 78 to 83. This epitope resides on the outer rim of the 30 A long spikes that protrude from the capsid shell. These spikes are four-helix bundles formed by the pairing of helix-turn-helix motifs from two subunits; by means of a tilting experiment, we have determined that this bundle is right-handed. Variants of the same protein present two clinically important and non-crossreactive antigens: core antigen (HBcAg), which appears early in infection as assembled capsids; and the sentinel e-antigen (HBeAg), a non-particulate form. Knowledge of the binding site of our anti-HBcAg antibody bears on the molecular basis of the distinction between the two antigens, which appears to reflect conformational differences between the assembled and unassembled states of the capsid protein dimer, in addition to epitope masking in capsids.
Conway
J F
JF
Laboratory of Structural Biology Research and Protein Expression Laboratory, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cheng
N
N
Zlotnick
A
A
Stahl
S J
SJ
Wingfield
P T
PT
Belnap
D M
DM
Kanngiesser
U
U
Noah
M
M
Steven
A C
AC
D000911:Antibodies, Monoclonal / Q000276:immunology; D002213:Capsid / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000737:chemistry / Q000276:immunology*; D006515:Hepatitis B virus / Q000737:chemistry / Q000276:immunology*; D008958:Models, Molecular; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens