3LH2

Crystal structure of HIV epitope-scaffold 4E10_1VI7A_S0_002_N 4E10 Fv complex

3LH2 の概要

• エントリーDOI: 10.2210/pdb3lh2/pdb
• 関連するPDBエントリー: 3LEF 3LF6 3LF9 3LG7 3LHP
• 分子名称: 4E10_1VI7A_S0_002_N (T88), Fv 4E10 heavy chain, Fv 4E10 light chain, ... (4 entities in total)
• 機能のキーワード: epitope-scaffold, immune system
• 由来する生物種: ARTIFICIAL GENE; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 141890.96

構造登録者

Holmes, M.A. (登録日: 2010-01-21, 公開日: 2010-09-22, 最終更新日: 2024-11-27)

主引用文献

Correia, B.E.,Ban, Y.E.,Holmes, M.A.,Xu, H.,Ellingson, K.,Kraft, Z.,Carrico, C.,Boni, E.,Sather, D.N.,Zenobia, C.,Burke, K.Y.,Bradley-Hewitt, T.,Bruhn-Johannsen, J.F.,Kalyuzhniy, O.,Baker, D.,Strong, R.K.,Stamatatos, L.,Schief, W.R.
Computational Design of Epitope-Scaffolds Allows Induction of Antibodies Specific for a Poorly Immunogenic HIV Vaccine Epitope.
Structure, 18:1116-1126, 2010

PubMed Abstract: Broadly cross-reactive monoclonal antibodies define epitopes for vaccine development against HIV and other highly mutable viruses. Crystal structures are available for several such antibody-epitope complexes, but methods are needed to translate that structural information into immunogens that re-elicit similar antibodies. We describe a general computational method to design epitope-scaffolds in which contiguous structural epitopes are transplanted to scaffold proteins for conformational stabilization and immune presentation. Epitope-scaffolds designed for the poorly immunogenic but conserved HIV epitope 4E10 exhibited high epitope structural mimicry, bound with higher affinities to monoclonal antibody (mAb) 4E10 than the cognate peptide, and inhibited HIV neutralization by HIV+ sera. Rabbit immunization with an epitope-scaffold induced antibodies with structural specificity highly similar to mAb 4E10, an important advance toward elicitation of neutralizing activity. The results demonstrate that computationally designed epitope-scaffolds are valuable as structure-specific serological reagents and as immunogens to elicit antibodies with predetermined structural specificity.

PubMed: 20826338
DOI: 10.1016/j.str.2010.06.010

実験手法

X-RAY DIFFRACTION (2.65 Å)