Hepatitis B small surface antigen particles are octahedral

doi:10.1073/pnas.0505062102

Hepatitis B small surface antigen particles are octahedral

^*Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom; ^†Oxford Centre for Molecular Sciences, Central Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QH, United Kingdom; ^‡School of Biochemistry and Microbiology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, United Kingdom; ^§Biology Department, Brookhaven National Laboratory, Upton, NY 11973; and ^¶Division of Experimental Pathology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037

Edited by Robert A. Lamb, Northwestern University, Evanston, IL, and approved August 17, 2005 (received for review June 17, 2005)

Abstract

The infectious component of hepatitis B (HB) virus (HBV), the Dane particle, has a diameter of ≈44 nm and consists of a double-layered capsid particle enclosing a circular, incomplete double-stranded DNA genome. The outer capsid layer is formed from the HB surface antigen (HBsAg) and lipid, whereas the inner layer is formed from the HB core Ag assembled into an icosahedral structure. During chronic infection HBsAg is expressed in large excess as noninfectious quasispherical particles and tubules with ≈22-nm diameter. Here, we report cryo-EM reconstructions of spherical HBsAg particles at ≈12-Å resolution. We show that the particles possess different diameters and have separated them into two predominant populations, both of which have octahedral symmetry. Despite their differing diameters, the two forms of the particle have the same mass and are built through conformational switching of the same building block, a dimer of HBsAg. We propose that this conformational switching, combined with interactions with the underlying core, leads to the formation of HBV Dane particles of different sizes, dictated by the symmetry of the icosahedral core.

Footnotes

↵ ∥ To whom correspondence may be addressed. E-mail: dave{at}strubi.ox.ac.uk or d.j.rowlands{at}leeds.ac.uk.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: HB, hepatitis B; HBV, HB virus; Ag, antigen; HBcAg, HB core Ag; HBsAg, HB surface Ag; LHBsAg, long HBsAg; MHBsAg, medium HBsAg; SHBsAg, small HBsAg; mSHBsAg, mouse SHBsAg; STEM, scanning transmission EM; TMV, tobacco mosaic virus.
Data deposition: The reconstructions of HBSsAg particles reported herein have been deposited in the Macromolecular Structure Database, www.ebi.ac.uk/msd/index.html (accession nos. EMD-1158 and EMD-1159).