3EOB

Crystal structure the Fab fragment of Efalizumab in complex with LFA-1 I domain, Form II

3EOB の概要

• エントリーDOI: 10.2210/pdb3eob/pdb
• 関連するPDBエントリー: 3EO9 3EOA
• 分子名称: Efalizumab Fab fragment, light chain, Efalizumab Fab fragment, heavy chain, Integrin alpha-L, ... (4 entities in total)
• 機能のキーワード: efalizumab, fab, antibody, lfa-1, cd11a, i domain, alternative splicing, calcium, cell adhesion, glycoprotein, integrin, magnesium, membrane, polymorphism, receptor, transmembrane, immune system-cell adhesion complex, immune system/cell adhesion
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P20701
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 135863.55

構造登録者

Li, S.,Ding, J. (登録日: 2008-09-26, 公開日: 2009-04-14, 最終更新日: 2024-11-20)

主引用文献

Li, S.,Wang, H.,Peng, B.,Zhang, M.,Zhang, D.,Hou, S.,Guo, Y.,Ding, J.
Efalizumab binding to the LFA-1 alphaL I domain blocks ICAM-1 binding via steric hindrance.
Proc.Natl.Acad.Sci.USA, 106:4349-4354, 2009

PubMed Abstract: Lymphocyte function-associated antigen 1 (LFA-1) plays important roles in immune cell adhesion, trafficking, and activation and is a therapeutic target for the treatment of multiple autoimmune diseases. Efalizumab is one of the most efficacious antibody drugs for treating psoriasis, a very common skin disease, through inhibition of the binding of LFA-1 to the ligand intercellular adhesion molecule 1 (ICAM-1). We report here the crystal structures of the Efalizumab Fab alone and in complex with the LFA-1 alpha(L) I domain, which reveal the molecular mechanism of inhibition of LFA-1 by Efalizumab. The Fab binds with an epitope on the inserted (I) domain that is distinct from the ligand-binding site. Efalizumab binding blocks the binding of LFA-1 to ICAM-1 via steric hindrance between its light chain and ICAM-1 domain 2 and thus inhibits the activities of LFA-1. These results have important implications for the development of improved antibodies and new therapeutic strategies for the treatment of autoimmune diseases.

PubMed: 19258452
DOI: 10.1073/pnas.0810844106

実験手法

X-RAY DIFFRACTION (3.6 Å)