2GJJ

Crystal structure of a single chain antibody scA21 against Her2/ErbB2

2GJJ の概要

• エントリーDOI: 10.2210/pdb2gjj/pdb
• 分子名称: A21 single-chain antibody fragment against erbB2, GLYCEROL (3 entities in total)
• 機能のキーワード: ig family, scfv, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57284.81

構造登録者

Zhu, Z. (登録日: 2006-03-31, 公開日: 2006-10-01, 最終更新日: 2024-11-06)

主引用文献

Hu, S.,Zhu, Z.,Li, L.,Chang, L.,Li, W.,Cheng, L.,Teng, M.,Liu, J.
Epitope mapping and structural analysis of an anti-ErbB2 antibody A21: Molecular basis for tumor inhibitory mechanism
Proteins, 70:938-949, 2007

PubMed Abstract: Anti-ErbB2 antibodies targeting distinct epitopes can have different biological functions on cancer cells. A21 prepared by surface epitope masking (SEM) method is a tumor-inhibitory anti-ErbB2 monoclonal antibody. Previously we engineered a single chain chimeric antibody chA21 with potential for therapy of ErbB2-overexpressing tumors. Here, we mapped the A21 epitope on ErbB2 extracellular domain (ECD) by screening a combinatorial phage display peptide library, serial subdomain deletion, and mutagenesis scanning. X-ray crystal structure of the A21 scFv fragment at 2.1 A resolution was also determined. A molecular model of Ag-Ab complex was then constructed based on the crystal structures of the A21 scFv and ErbB2 ECD. Some of biological functions of the A21 mAb and its derivative antibodies including their tumor cell growth inhibition and effects on the expression, internalization, and phosphorylation of ErbB2 receptor were also investigated. The results showed that A21 recognized a conformational epitope comprising a large region mostly from ErbB2 extracellular subdomain I with several surface-exposed residues important for the binding affinity. These data provide unique functional properties of A21 that are quite different from two broadly used anti-ErbB2 mAbs, Herceptin and 2C4. It suggested that the A21 epitope may be another valuable target for designing new anti-ErbB2 therapeutics.

PubMed: 17847085
DOI: 10.1002/prot.21551

実験手法

X-RAY DIFFRACTION (2.1 Å)