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  • The EMBO Journal (2002) 21, 876 - 884
  • doi:10.1093/emboj/21.5.876

The morphogenic linker peptide of HBV capsid protein forms a mobile array on the interior surface

Norman R. Watts1, James F. Conway2,3, Naiqian Cheng2, Stephen J. Stahl1, David M. Belnap2, Alasdair C. Steven2 and Paul T. Wingfield1

  1. Protein Expression Laboratory, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Building 50, Room 1517, 50 South drive MSC 8025, National Institutes of Health, Bethesda, MD 20892-8025, USA
  2. Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Building 50, Room 1517, 50 South drive MSC 8025, National Institutes of Health, Bethesda, MD 20892-8025, USA
  3. Institut de Biologie Structurale J.-P.Ebel, 41 rue Jules Horowitz, F-38027 Grenoble, France

Correspondence to:

Alasdair C. Steven, E-mail: Alasdair_Steven@nih.gov

Received 16 August 2001; Accepted 10 January 2002; Revised 10 January 2002

Many capsid proteins have peptides that influence their assembly. In hepatitis B virus capsid protein, the peptide STLPETTVV, linking the shell-forming 'core' domain and the nucleic acid-binding 'protamine' domain, has such a role. We have studied its morphogenic properties by permuting its sequence, substituting it with an extraneous peptide, deleting it to directly fuse the core and protamine domains and assembling core domain dimers with added linker peptides. The peptide was found to be necessary for the assembly of protamine domain-containing capsids, although its size-determining effect tolerates some modifications. Although largely invisible in a capsid crystal structure, we could visualize linker peptides by cryo-EM difference imaging: they emerge on the inner surface and extend from the capsid protein dimer interface towards the adjacent symmetry axis. A closely sequence-similar peptide in cellobiose dehydrogenase, which has an extended conformation, offers a plausible prototype. We propose that linker peptides are attached to the capsid inner surface as hinged struts, forming a mobile array, an arrangement with implications for morphogenesis and the management of encapsidated nucleic acid.

  • Keywords:

    • core antigen,
    • cryo-electron microscopy,
    • hepatitis B virus,
    • nucleic acid packaging,
    • nucleocapsid morphogenesis