7T98

Crystal structure of engineered CYS-CYS fab dimer VL-108 (LC33)

7T98 の概要

• エントリーDOI: 10.2210/pdb7t98/pdb
• 分子名称: FAB Heavy Chain, FAB Light Chain (3 entities in total)
• 機能のキーワード: immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95658.76

構造登録者

Harris, S.F.,Boenig, G.D.L. (登録日: 2021-12-18, 公開日: 2022-10-12, 最終更新日: 2024-10-30)

主引用文献

Yin, Y.,Romei, M.G.,Sankar, K.,Pal, L.R.,Hoi, K.H.,Yang, Y.,Leonard, B.,De Leon Boenig, G.,Kumar, N.,Matsumoto, M.,Payandeh, J.,Harris, S.F.,Moult, J.,Lazar, G.A.
Antibody interfaces revealed through structural mining.
Comput Struct Biotechnol J, 20:4952-4968, 2022

PubMed Abstract: Antibodies are fundamental effectors of humoral immunity, and have become a highly successful class of therapeutics. There is increasing evidence that antibodies utilize transient homotypic interactions to enhance function, and elucidation of such interactions can provide insights into their biology and new opportunities for their optimization as drugs. Yet the transitory nature of weak interactions makes them difficult to investigate. Capitalizing on their rich structural data and high conservation, we have characterized all the ways that antibody fragment antigen-binding (Fab) regions interact crystallographically. This approach led to the discovery of previously unrealized interfaces between antibodies. While diverse interactions exist, β-sheet dimers and variable-constant elbow dimers are recurrent motifs. Disulfide engineering enabled interactions to be trapped and investigated structurally and functionally, providing experimental validation of the interfaces and illustrating their potential for optimization. This work provides first insight into previously undiscovered oligomeric interactions between antibodies, and enables new opportunities for their biotherapeutic optimization.

PubMed: 36147680
DOI: 10.1016/j.csbj.2022.08.048

実験手法

X-RAY DIFFRACTION (2.97 Å)