5N88

Crystal structure of antibody bound to viral protein

5N88 の概要

• エントリーDOI: 10.2210/pdb5n88/pdb
• 分子名称: VH59 antibody, PC4 and SFRS1-interacting protein, ... (4 entities in total)
• 機能のキーワード: mll: hiv: intracellular antibody: integrase: ledgf, aids, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 46424.86

構造登録者

Bao, L.,Hannon, C.,Cruz-Migoni, A.,Ptchelkine, D.,Sun, M.-y.,Derveni, M.,Bunjobpol, W.,Chambers, J.S.,Simmons, A.,Phillips, S.E.V.,Rabbitts, T.H. (登録日: 2017-02-23, 公開日: 2017-12-20, 最終更新日: 2024-10-16)

主引用文献

Bao, L.,Hannon, C.,Cruz-Mignoni, A.,Ptchelkine, D.,Sun, M.Y.,Miller, A.,Bunjobpol, W.,Quevedo, C.E.,Derveni, M.,Chambers, J.,Simmons, A.,Phillips, S.E.V.,Rabbitts, T.H.
Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.
Sci Rep, 7:16869-16869, 2017

PubMed Abstract: Preventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for anti-viral treatment for AIDS. We have used Intracellular Antibody Capture technology to isolate a single VH antibody domain that binds to LEDGF. The crystal structure of the LEDGF-VH complex reveals that the single domain antibody mimics the effect of binding of HIV integrase to LEDGF which is crucial for HIV propagation. CD4-expressing T cell lines were constructed to constitutively express the LEDGF-binding VH and these cells showed interference with HIV viral replication, assayed by virus capsid protein p24 production. Therefore, pre-conditioning cells to express antibody fragments confers effective intracellular immunization for preventing chronic viral replication and can be a way to prevent HIV spread in infected patients. This raises the prospect that intracellular immunization strategies that focus on cellular components of viral integrase protein interactions can be used to combat the problems associated with latent HIV virus re-emergence in patients. New genome editing development, such as using CRISPR/cas9, offer the prospect intracellularly immunized T cells in HIV+ patients.

PubMed: 29203900
DOI: 10.1038/s41598-017-16742-2

実験手法

X-RAY DIFFRACTION (1.7 Å)