Structural highlights
Function
[CAPSD_HBVD3] Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with a icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions.[HAMAP-Rule:MF_04076] Encapsidates hepatitis delta genome.[HAMAP-Rule:MF_04076]
Publication Abstract from PubMed
Hepatitis B virus is a major human pathogen that consists of a viral genome surrounded by an icosahedrally ordered core protein and a polymorphic, lipidic envelope that is densely packed with surface proteins. A point mutation in the core protein in which a phenylalanine at position 97 is exchanged for a smaller leucine leads to premature envelopment of the capsid before the genome maturation is fully completed. We have used electron cryo-microscopy and image processing to investigate how the point mutation affects the structure of the capsid at 2.6- to 2.8A-resolution. We found that in the mutant the smaller side chain at position 97 is displaced, increasing the size of an adjacent pocket in the center of the spikes of the capsid. In the mutant, this pocket is filled with an unknown density. Phosphorylation of serine residues in the unresolved C-terminal domain of the mutant leaves the structure of the ordered capsid largely unchanged. However, we were able to resolve several previously unresolved residues downstream of proline 144 that precede the phosphorylation-sites. These residues pack against the neighboring subunits and increase the inter-dimer contact suggesting that the C-termini play an important role in capsid stabilization and provide a much larger interaction interface than previously observed.
Structure of Mutant Hepatitis B Core Protein Capsids with Premature Secretion Phenotype.,Bottcher B, Nassal M J Mol Biol. 2018 Dec 7;430(24):4941-4954. doi: 10.1016/j.jmb.2018.10.018. Epub, 2018 Oct 27. PMID:30539760[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bottcher B, Nassal M. Structure of Mutant Hepatitis B Core Protein Capsids with Premature Secretion Phenotype. J Mol Biol. 2018 Dec 7;430(24):4941-4954. doi: 10.1016/j.jmb.2018.10.018. Epub, 2018 Oct 27. PMID:30539760 doi:http://dx.doi.org/10.1016/j.jmb.2018.10.018
