4XZU

Crystal Structure of the Human Factor VIII C2 Domain in Complex with Murine 3E6 Inhibitory Antibody

4XZU の概要

• エントリーDOI: 10.2210/pdb4xzu/pdb
• 分子名称: 3E6 antibody Fab heavy chain, 3E6 antibody Fab light chain, Coagulation factor VIII, ... (5 entities in total)
• 機能のキーワード: immunoglobulin, blood coagulation, antibody, discoidin, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 128785.09

構造登録者

Spiegel, P.C.,Wuerth, M.E. (登録日: 2015-02-05, 公開日: 2015-12-09, 最終更新日: 2024-10-23)

主引用文献

Wuerth, M.E.,Cragerud, R.K.,Clint Spiegel, P.
Structure of the Human Factor VIII C2 Domain in Complex with the 3E6 Inhibitory Antibody.
Sci Rep, 5:17216-17216, 2015

PubMed Abstract: Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into "classical" and "non-classical" inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conserved when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.

PubMed: 26598467
DOI: 10.1038/srep17216

実験手法

X-RAY DIFFRACTION (2.61 Å)