6CFE

Crystal structure of C2S5: A computationally designed immunogen to target Carbohydrate-Occluded Epitopes on the HIV envelope

6CFE の概要

• エントリーDOI: 10.2210/pdb6cfe/pdb
• 分子名称: Mutant of Apolipoprotein E3 (APO-E3) (2 entities in total)
• 機能のキーワード: immunogen, hiv-1, gp120, protein design, mutant of apolipoprotein e3 (apo-e3), lipid transport
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18643.03

構造登録者

Zhu, C.,Ke, H.M.,Swanstrom, R.,Dokholyan, N.V. (登録日: 2018-02-14, 公開日: 2019-02-06, 最終更新日: 2023-10-04)

主引用文献

Zhu, C.,Dukhovlinova, E.,Council, O.,Ping, L.,Faison, E.M.,Prabhu, S.S.,Potter, E.L.,Upton, S.L.,Yin, G.,Fay, J.M.,Kincer, L.P.,Spielvogel, E.,Campbell, S.L.,Benhabbour, S.R.,Ke, H.,Swanstrom, R.,Dokholyan, N.V.
Rationally designed carbohydrate-occluded epitopes elicit HIV-1 Env-specific antibodies.
Nat Commun, 10:948-948, 2019

PubMed Abstract: An array of carbohydrates masks the HIV-1 surface protein Env, contributing to the evasion of humoral immunity. In most HIV-1 isolates 'glycan holes' occur due to natural sequence variation, potentially revealing the underlying protein surface to the immune system. Here we computationally design epitopes that mimic such surface features (carbohydrate-occluded neutralization epitopes or CONE) of Env through 'epitope transplantation', in which the target region is presented on a carrier protein scaffold with preserved structural properties. Scaffolds displaying the four CONEs are examined for structure and immunogenicity. Crystal structures of two designed proteins reflect the computational models and accurately mimic the native conformations of CONEs. The sera from rabbits immunized with several CONE immunogens display Env binding activity. Our method determines essential structural elements for targets of protective antibodies. The ability to design immunogens with high mimicry to viral proteins also makes possible the exploration of new templates for vaccine development.

PubMed: 30814513
DOI: 10.1038/s41467-019-08876-w

実験手法

X-RAY DIFFRACTION (1.994 Å)