6CWT

Hepatitis B core-antigen in complex with Fab e21

6CWT の概要

• エントリーDOI: 10.2210/pdb6cwt/pdb
• 分子名称: Fab e21 heavy chain, Fab e21 light chain, Capsid protein (3 entities in total)
• 機能のキーワード: hepatitis b virus, fab, core dimer, nucleocapsid, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Oryctolagus cuniculus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 128763.84

構造登録者

Eren, E.,Steven, A.C.,Wingfield, P.T. (登録日: 2018-03-30, 公開日: 2018-08-29, 最終更新日: 2024-10-23)

主引用文献

Eren, E.,Watts, N.R.,Dearborn, A.D.,Palmer, I.W.,Kaufman, J.D.,Steven, A.C.,Wingfield, P.T.
Structures of Hepatitis B Virus Core- and e-Antigen Immune Complexes Suggest Multi-point Inhibition.
Structure, 26:1314-, 2018

PubMed Abstract: Hepatitis B virus (HBV) is the leading cause of liver disease worldwide. While an adequate vaccine is available, current treatment options are limited, not highly effective, and associated with adverse effects, encouraging the development of alternative therapeutics. The HBV core gene encodes two different proteins: core, which forms the viral nucleocapsid, and pre-core, which serves as an immune modulator with multiple points of action. The two proteins mostly have the same sequence, although they differ at their N and C termini and in their dimeric arrangements. Previously, we engineered two human-framework antibody fragments (Fab/scFv) with nano- to picomolar affinities for both proteins. Here, by means of X-ray crystallography, analytical ultracentrifugation, and electron microscopy, we demonstrate that the antibodies have non-overlapping epitopes and effectively block biologically important assemblies of both proteins. These properties, together with the anticipated high tolerability and long half-lives of the antibodies, make them promising therapeutics.

PubMed: 30100358
DOI: 10.1016/j.str.2018.06.012

実験手法

X-RAY DIFFRACTION (3.151 Å)