6CVK

Hepatitis B e-antigen in complex with scFv e13

Summary for 6CVK

• Entry DOI: 10.2210/pdb6cvk/pdb
• Descriptor: Single chain variable fragment (scFv) e13, Capsid protein (3 entities in total)
• Functional Keywords: hepatitis b, single chain variable fragment, e-antigen, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Oryctolagus cuniculus; More
• Total number of polymer chains: 4
• Total formula weight: 89352.31

Authors

Eren, E.,Steven, A.C.,Wingfield, P.T. (deposition date: 2018-03-28, release date: 2018-08-29, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.38 Å)