3ET9

Crystal structure of the engineered neutralizing antibody 1H

3ET9 の概要

• エントリーDOI: 10.2210/pdb3et9/pdb
• 関連するPDBエントリー: 3ESU 3ESV 3ETB
• 分子名称: Antibody 1H light chain and antibody 1H heavy chain linked with a synthetic (GGGGS)4 linker (2 entities in total)
• 機能のキーワード: single-chain fv, monoclonal antibody, immunoglobulin, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26758.62

構造登録者

Leysath, C.E.,Monzingo, A.F.,Barnett, J.,Iverson, B.L.,Georgiou, G.,Robertus, J.D. (登録日: 2008-10-07, 公開日: 2009-04-28, 最終更新日: 2024-11-06)

主引用文献

Leysath, C.E.,Monzingo, A.F.,Maynard, J.A.,Barnett, J.,Georgiou, G.,Iverson, B.L.,Robertus, J.D.
Crystal structure of the engineered neutralizing antibody m18 complexed to domain 4 of the anthrax protective antigen.
J.Mol.Biol., 387:680-693, 2009

PubMed Abstract: The virulence of Bacillus anthracis is critically dependent on the cytotoxic components of the anthrax toxin, lethal factor (LF) and edema factor (EF). LF and EF gain entry into host cells through interactions with the protective antigen (PA), which binds to host cellular receptors such as CMG2. Antibodies that neutralize PA have been shown to confer protection in animal models and are undergoing intense clinical development. A murine monoclonal antibody, 14B7, has been reported to interact with domain 4 of PA (PAD4) and block its binding to CMG2. More recently, the 14B7 antibody was used as the platform for the selection of very high affinity, single-chain antibodies that have tremendous potential as a combination anthrax prophylactic and treatment. Here, we report the high-resolution X-ray structures of three high-affinity, single-chain antibodies in the 14B7 family; 14B7 and two high-affinity variants 1H and M18. In addition, we present the first neutralizing antibody-PA structure, M18 in complex with PAD4 at 3.8 A resolution. These structures provide insights into the mechanism of neutralization, and the effect of various mutations on antibody affinity, and enable a comparison between the binding of the M18 antibody and CMG2 with PAD4.

PubMed: 19361425
DOI: 10.1016/j.jmb.2009.02.003

実験手法

X-RAY DIFFRACTION (2.8 Å)