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TitleStructural basis for nuclear import of hepatitis B virus (HBV) nucleocapsid core.
Journal, issue, pagesSci Adv, Vol. 10, Issue 2, Page eadi7606, Year 2024
Publish dateJan 12, 2024
AuthorsRuoyu Yang / Ying-Hui Ko / Fenglin Li / Ravi K Lokareddy / Chun-Feng David Hou / Christine Kim / Shelby Klein / Santiago Antolínez / Juan F Marín / Carolina Pérez-Segura / Martin F Jarrold / Adam Zlotnick / Jodi A Hadden-Perilla / Gino Cingolani /
PubMed AbstractNuclear 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 ...Nuclear 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 α1 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 α1. The binding of 30 importin α1/β1 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.
External linksSci Adv / PubMed:38198557 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.99 - 3.95 Å
Structure data

EMDB-29756, PDB-8g5v:
Empty capsid of Hepatitis B virus
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-29785, PDB-8g6v:
Hepatitis B virus capsid bound to importin alpha1/beta heterodimer
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-29858, PDB-8g8y:
Hepatitis B virus capsid bound to importin alpha1
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-29936, PDB-8gcn:
CRYO-EM STRUCTURE OF IMPORTIN ALPHA1/BETA HETERODIMER
Method: EM (single particle) / Resolution: 3.95 Å

PDB-7umi:
Importin a1 bound to Cp183-CTD
Method: X-RAY DIFFRACTION / Resolution: 1.99 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • hepatitis b virus
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsPROTEIN TRANSPORT / nuclear import / viral replication / peptide binding / nuclear localization signal binding / NUCLEAR PROTEIN / VIRUS LIKE PARTICLE / Virus capsid / complex formed by viral capsid and importin / Capsid formed by Cp183 when bound to importin alpha1 / TRANSPORT PROTEIN / Importins

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