7JPH

Crystal structure of EBOV glycoprotein with modified HR1c and HR2 stalk at 3.2 A resolution

7JPH の概要

• エントリーDOI: 10.2210/pdb7jph/pdb
• 分子名称: Envelope glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: ebola glycoprotein, viral protein
• 由来する生物種: Ebola virus - Mayinga, Zaire, 1976 (ZEBOV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53094.31

構造登録者

Chaudhary, A.,Stanfield, R.L.,Wilson, I.A.,Zhu, J. (登録日: 2020-08-08, 公開日: 2021-04-07, 最終更新日: 2024-11-20)

主引用文献

He, L.,Chaudhary, A.,Lin, X.,Sou, C.,Alkutkar, T.,Kumar, S.,Ngo, T.,Kosviner, E.,Ozorowski, G.,Stanfield, R.L.,Ward, A.B.,Wilson, I.A.,Zhu, J.
Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines.
Nat Commun, 12:2633-2633, 2021

PubMed Abstract: Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1) regions to GP metastability. Specific stalk and HR1 modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1 exert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display.

PubMed: 33976149
DOI: 10.1038/s41467-021-22867-w

実験手法

X-RAY DIFFRACTION (3.195 Å)