8g8y
Hepatitis B virus capsid bound to importin alpha1
Structural highlights
FunctionA0A1B2G2S7_HBV May regulate immune response to the intracellular capsid in acting as a T-cell tolerogen, by having an immunoregulatory effect which prevents destruction of infected cells by cytotoxic T-cells.[RuleBase:RU361253] Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an 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 capsids 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 stuck 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 genomes for transcription, or bud through the endoplasmic reticulum to provide new virions.[HAMAP-Rule:MF_04076] Publication Abstract from PubMedNuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin alpha1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 promotes CTD compaction but does not affect the affinity for importin alpha1. The binding of 30 importin alpha1/beta1 augments HBV capsid diameter to ~620 angstroms, close to the maximum size trafficable through the NPC. We propose that phosphorylation favors CTD externalization and prompts its compaction at the capsid surface, exposing the NLS to importins. Structural basis for nuclear import of hepatitis B virus (HBV) nucleocapsid core.,Yang R, Ko YH, Li F, Lokareddy RK, Hou CD, Kim C, Klein S, Antolinez S, Marin JF, Perez-Segura C, Jarrold MF, Zlotnick A, Hadden-Perilla JA, Cingolani G Sci Adv. 2024 Jan 12;10(2):eadi7606. doi: 10.1126/sciadv.adi7606. Epub 2024 Jan , 10. PMID:38198557[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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