6VEH

Computationally designed C3-symmetric homotrimer from HEAT repeat protein

6VEH の概要

• エントリーDOI: 10.2210/pdb6veh/pdb
• 分子名称: HEAT repeat domain-containing protein (2 entities in total)
• 機能のキーワード: designed protein, vaccine, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21022.39

構造登録者

Bick, M.J.,Ueda, G.,Baker, D. (登録日: 2020-01-02, 公開日: 2020-08-05, 最終更新日: 2024-11-20)

主引用文献

Ueda, G.,Antanasijevic, A.,Fallas, J.A.,Sheffler, W.,Copps, J.,Ellis, D.,Hutchinson, G.B.,Moyer, A.,Yasmeen, A.,Tsybovsky, Y.,Park, Y.J.,Bick, M.J.,Sankaran, B.,Gillespie, R.A.,Brouwer, P.J.,Zwart, P.H.,Veesler, D.,Kanekiyo, M.,Graham, B.S.,Sanders, R.W.,Moore, J.P.,Klasse, P.J.,Ward, A.B.,King, N.P.,Baker, D.
Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens.
Elife, 9:-, 2020

PubMed Abstract: Multivalent presentation of viral glycoproteins can substantially increase the elicitation of antigen-specific antibodies. To enable a new generation of anti-viral vaccines, we designed self-assembling protein nanoparticles with geometries tailored to present the ectodomains of influenza, HIV, and RSV viral glycoprotein trimers. We first designed trimers tailored for antigen fusion, featuring N-terminal helices positioned to match the C termini of the viral glycoproteins. Trimers that experimentally adopted their designed configurations were incorporated as components of tetrahedral, octahedral, and icosahedral nanoparticles, which were characterized by cryo-electron microscopy and assessed for their ability to present viral glycoproteins. Electron microscopy and antibody binding experiments demonstrated that the designed nanoparticles presented antigenically intact prefusion HIV-1 Env, influenza hemagglutinin, and RSV F trimers in the predicted geometries. This work demonstrates that antigen-displaying protein nanoparticles can be designed from scratch, and provides a systematic way to investigate the influence of antigen presentation geometry on the immune response to vaccination.

PubMed: 32748788
DOI: 10.7554/eLife.57659

実験手法

X-RAY DIFFRACTION (2.303 Å)