PDBsum entry 1a92

Leucine zipper

PDB id: 1a92

Contents

Protein chains

50 a.a. *

Waters ×114

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Structural basis of the oligomerization of hepatitis delta antigen.
• Authors: H.J.Zuccola, J.E.Rozzelle, S.M.Lemon, B.W.Erickson, J.M.Hogle.
• Ref.: Structure, 1998, 6, 821-830. [DOI no: 10.1016/S0969-2126(98)00084-7]
• PubMed id: 9687364

Abstract

BACKGROUND: The hepatitis D virus (HDV) is a small satellite virus of hepatitis B virus (HBV). Coinfection with HBV and HDV causes severe liver disease in humans. The small 195 amino-acid form of the hepatitis delta antigen (HDAg) functions as a trans activator of HDV replication. A larger form of the protein containing a 19 amino acid C-terminal extension inhibits viral replication. Both of these functions are mediated in part by a stretch of amino acids predicted to form a coiled coil (residues 13-48) that is common to both forms. It is believed that HDAg forms dimers and higher ordered structures through this coiled-coil region. RESULTS: The high-resolution crystal structure of a synthetic peptide corresponding to residues 12 to 60 of HDAg has been solved. The peptide forms an antiparallel coiled coil, with hydrophobic residues near the termini of each peptide forming an extensive hydrophobic core with residues C-terminal to the coiled-coil domain in the dimer protein. The structure shows how HDAg forms dimers, but also shows the dimers forming an octamer that forms a 50 A ring lined with basic sidechains. This is confirmed by cross-linking studies of full-length recombinant small HDAg. CONCLUSIONS: HDAg dimerizes through an antiparallel coiled coil. Dimers then associate further to form octamers through residues in the coiled-coil domain and residues C-terminal to this region. Our findings suggest that the structure of HDAg represents a previously unseen organization of a nucleocapsid protein and raise the possibility that the N terminus may play a role in binding the viral RNA.

Figure 3.
Figure 3. Overall organization of the HDAg dimer. (a) Ca trace of the peptide d12-60(Y). The three regions of the peptide are color-coded: A pink; B green; and C purple. The two monomers form an antiparallel coiled coil. The individual helix takes a sharp bend at Pro49. (b) Ribbon diagram of the view in (a) rotated 90° along the horizontal axis. The sidechains have been added and the C region of the peptide (residues 50-60(Y)) has been removed for clarity. Sidechains are color-coded: hydrophobic, gray; polar, yellow; acidic, red; and basic, blue. Although the majority of the hydrophobic sidechains are packed in the interior of the coiled coil, Trp20 is flipped out of the core of the long helix. The figure also illustrates that the two helices clearly wrap around one another. (c) The amino-acid sequence of the long helix formed from residues 12-48 displayed in the antiparallel orientation of the peptide. The letters above the amino-acid sequence represent the heptad repeat (abcdefg)[n] where the a and d residues tend to be hydrophobic. Residues involved in the heptad repeat at the a and d positions are shown in bold.

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 821-830) copyright 1998.

Secondary reference #1

• Title: Self-Association of a synthetic peptide from the n terminus of the hepatitis delta virus protein into an immunoreactive alpha-Helical multimer.
• Authors: J.E.Rozzelle, J.G.Wang, D.S.Wagner, B.W.Erickson, S.M.Lemon.
• Ref.: Proc Natl Acad Sci U S A, 1995, 92, 382-386. [DOI no: 10.1073/pnas.92.2.382]
• PubMed id: 7831295