6WFS

Cryo-EM Structure of Hepatitis B virus T=4 capsid in complex with the antiviral molecule DBT1

6WFS の概要

• エントリーDOI: 10.2210/pdb6wfs/pdb
• EMDBエントリー: 21653 21654 21655
• 分子名称: Capsid protein, 11-oxo-N-[2-(4-sulfamoylphenyl)ethyl]-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide (2 entities in total)
• 機能のキーワード: capsid, antiviral, hbv, virus like particle
• 由来する生物種: Hepatitis B virus genotype D subtype adw (isolate United Kingdom/adyw/1979)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 68978.55

構造登録者

Schlicksup, C.,Laughlin, P.,Dunkelbarger, S.,Wang, J.C.,Zlotnick, A. (登録日: 2020-04-03, 公開日: 2020-06-03, 最終更新日: 2024-03-06)

主引用文献

Schlicksup, C.J.,Laughlin, P.,Dunkelbarger, S.,Wang, J.C.,Zlotnick, A.
Local Stabilization of Subunit-Subunit Contacts Causes Global Destabilization of Hepatitis B Virus Capsids.
Acs Chem.Biol., 15:1708-1717, 2020

PubMed Abstract: Development of antiviral molecules that bind virion is a strategy that remains in its infancy, and the details of their mechanisms are poorly understood. Here we investigate the behavior of DBT1, a dibenzothiazepine that specifically interacts with the capsid protein of hepatitis B virus (HBV). We found that DBT1 stabilizes protein-protein interaction, accelerates capsid assembly, and can induce formation of aberrant particles. Paradoxically, DBT1 can cause preformed capsids to dissociate. These activities may lead to (i) assembly of empty and defective capsids, inhibiting formation of new virus, and (ii) disruption of mature viruses, which are metastable, to inhibit new infection. Using cryo-electron microscopy, we observed that DBT1 led to asymmetric capsids where well-defined DBT1 density was bound at all intersubunit contacts. These results suggest that DBT1 can support assembly by increasing buried surface area but induce disassembly of metastable capsids by favoring asymmetry to induce structural defects.

PubMed: 32369333
DOI: 10.1021/acschembio.0c00320

実験手法

ELECTRON MICROSCOPY (4.6 Å)