8THZ

CryoEM structure of neutralizing antibodies CBH-7 and HC84.26 in complex with Hepatitis C virus envelope glycoprotein E2

8THZ の概要

• エントリーDOI: 10.2210/pdb8thz/pdb
• EMDBエントリー: 41275
• 分子名称: CBH-7 Heavy chain, CBH-7 Light chain, envelope glycoprotein E2, ... (9 entities in total)
• 機能のキーワード: immune system, vaccine target, e2 glycoprotein, hcv, ternary complex, antiviral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 141824.25

構造登録者

Shahid, S.,Jiang, L.,Liu, Y.,Hasan, S.S.,Mariuzza, R.A. (登録日: 2023-07-18, 公開日: 2024-07-24, 最終更新日: 2025-07-09)

主引用文献

Shahid, S.,Karade, S.S.,Hasan, S.S.,Yin, R.,Jiang, L.,Liu, Y.,Felbinger, N.,Kulakova, L.,Toth, E.A.,Keck, Z.Y.,Foung, S.K.H.,Fuerst, T.R.,Pierce, B.G.,Mariuzza, R.A.
Cryo-EM structures of HCV E2 glycoprotein bound to neutralizing and non-neutralizing antibodies determined using bivalent Fabs as fiducial markers.
Commun Biol, 8:825-825, 2025

PubMed Abstract: Global elimination of hepatitis C virus (HCV) will require an effective cross-genotype vaccine. The HCV E2 envelope glycoprotein is the main target of neutralizing antibodies but also contains epitopes that elicit non-neutralizing antibodies which may provide protection through Fc effector functions rather than direct neutralization. We determined cryo-EM structures of a broadly neutralizing antibody, a moderately neutralizing antibody, and a non-neutralizing antibody bound to E2 to resolutions of 3.8, 3.3, and 3.7 Å, respectively. Whereas the broadly neutralizing antibody targeted the front layer of E2 and the non-neutralizing antibody targeted the back layer, the moderately neutralizing antibody straddled both front and back layers, and thereby defined a new neutralizing epitope on E2. The small size of complexes between conventional (monovalent) Fabs and E2 (~110 kDa) presented a challenge for cryo-EM. Accordingly, we engineered bivalent versions of E2-specific Fabs that doubled the size of Fab-E2 complexes and conferred highly identifiable shapes to the complexes that facilitated particle selection and orientation for image processing. This study validates bivalent Fabs as new fiducial markers for cryo-EM analysis of small proteins such as HCV E2 and identifies a new target epitope for vaccine development.

PubMed: 40442315
DOI: 10.1038/s42003-025-08239-w

実験手法

ELECTRON MICROSCOPY (3.25 Å)