5XJ3

Complex structure of ipilimumab-scFv and CTLA-4

5XJ3 の概要

• エントリーDOI: 10.2210/pdb5xj3/pdb
• 関連するPDBエントリー: 5XJ4
• 分子名称: ipilimumab-VH, ipilimumab-VL, Cytotoxic T-lymphocyte protein 4 (3 entities in total)
• 機能のキーワード: ipilimumab, ctla-4, complex structure, immune system
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein : P16410
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 154673.56

構造登録者

He, M.,Chai, Y.,Qi, J.,Tong, Z.,Tan, S.,Gao, G.F. (登録日: 2017-04-29, 公開日: 2018-04-25, 最終更新日: 2024-10-23)

主引用文献

He, M.,Chai, Y.,Qi, J.,Zhang, C.W.H.,Tong, Z.,Shi, Y.,Yan, J.,Tan, S.,Gao, G.F.
Remarkably similar CTLA-4 binding properties of therapeutic ipilimumab and tremelimumab antibodies
Oncotarget, 8:67129-67139, 2017

PubMed Abstract: Monoclonal antibody based immune checkpoint blockade therapies have achieved clinical successes in management of malignant tumors. As the first monoclonal antibody targeting immune checkpoint molecules entered into clinics, the molecular basis of ipilimumab-based anti-CTLA-4 blockade has not yet been fully understood. In the present study, we report the complex structure of ipilimumab and CTLA-4. The complex structure showed similar contributions from VH and VL of ipilimumab in binding to CTLA-4 front β-sheet strands. The blockade mechanism of ipilimumab is that the strands of CTLA-4 contributing to the binding to B7-1 or B7-2 were occupied by ipilimumab and thereafter prevents the binding of B7-1 or B7-2 to CTLA-4. Though ipilimumab binds to the same epitope with tremelimumab on CTLA-4 with similar binding affinity, the higher dissociation rate of ipilimumab may indicate the dynamic binding to CTLA-4, which may affect its pharmacokinetics. The molecular basis of ipilimumab-based anti-CTLA-4 blockade and comparative study of the binding characteristics of ipilimumab and tremelimumab would shed light for the discovery of small molecular inhibitors and structure-based monoclonal antibody optimization or new biologics.

PubMed: 28978021
DOI: 10.18632/oncotarget.18004

実験手法

X-RAY DIFFRACTION (3.2 Å)