5EA0

Structure of the antibody 7968 with human complement factor H-derived peptide

5EA0 の概要

• エントリーDOI: 10.2210/pdb5ea0/pdb
• 分子名称: Heavy chain of antibody 7968 Fab fragment, Light chain of antibody 7968 Fab fragment, Complement factor H-related protein 2, ... (4 entities in total)
• 機能のキーワード: complement factor h cfh scr19 scr19-20, immune system
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Secreted: P36980
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49355.16

構造登録者

Bushey, R.T.,Moody, M.A.,Nicely, N.I.,Alam, S.M.,Haynes, B.F.,Winkler, M.T.,Gottlin, E.B.,Campa, M.J.,Liao, H.-X.,Patz Jr., E.F. (登録日: 2015-10-15, 公開日: 2016-05-25, 最終更新日: 2024-11-06)

主引用文献

Bushey, R.T.,Moody, M.A.,Nicely, N.L.,Haynes, B.F.,Alam, S.M.,Keir, S.T.,Bentley, R.C.,Roy Choudhury, K.,Gottlin, E.B.,Campa, M.J.,Liao, H.X.,Patz, E.F.
A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.
Cell Rep, 15:1505-1513, 2016

PubMed Abstract: Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic membrane attack complexes on self-surfaces. In an effort to translate these findings into a biologic therapy for cancer, we isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. The co-crystal structure of a CFH antibody-target complex shows a conformational change in the target relative to the native structure. This recombinant CFH antibody causes complement activation and release of anaphylatoxins, promotes CDC of tumor cell lines, and inhibits tumor growth in vivo. The isolation of anti-tumor antibodies derived from single human B cells represents an alternative paradigm in antibody drug discovery.

PubMed: 27160908
DOI: 10.1016/j.celrep.2016.04.038

実験手法

X-RAY DIFFRACTION (2 Å)