6Z6V

Globular head of C1q in complex with the nanobody C1qNb75

6Z6V の概要

• エントリーDOI: 10.2210/pdb6z6v/pdb
• 関連するPDBエントリー: 5hzf
• 分子名称: Complement C1q subcomponent subunit A, Complement C1q subcomponent subunit B, Complement C1q subcomponent subunit C, ... (6 entities in total)
• 機能のキーワード: complement, antibody, nanobody, c1q, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 122353.12

構造登録者

Laursen, N.S.,Andersen, G.R. (登録日: 2020-05-29, 公開日: 2020-06-10, 最終更新日: 2024-11-13)

主引用文献

Laursen, N.S.,Pedersen, D.V.,Gytz, H.,Zarantonello, A.,Bernth Jensen, J.M.,Hansen, A.G.,Thiel, S.,Andersen, G.R.
Functional and Structural Characterization of a Potent C1q Inhibitor Targeting the Classical Pathway of the Complement System.
Front Immunol, 11:1504-1504, 2020

PubMed Abstract: The classical pathway of complement is important for protection against pathogens and in maintaining tissue homeostasis, but excessive or aberrant activation is directly linked to numerous pathologies. We describe the development and characterization of C1qNb75, a single domain antibody (nanobody) specific for C1q, the pattern recognition molecule of the classical pathway. C1qNb75 binds to the globular head modules of human C1q with sub-nanomolar affinity and impedes classical pathway mediated hemolysis by IgG and IgM. Crystal structure analysis revealed that C1qNb75 recognizes an epitope primarily located in the C1q B-chain that overlaps with the binding sites of IgG and IgM. Thus, C1qNb75 competitively prevents C1q from binding to IgG and IgM causing blockade of complement activation by the classical pathway. Overall, C1qNb75 represents a high-affinity nanobody-based inhibitor of IgG- and IgM-mediated activation of the classical pathway and may serve as a valuable reagent in mechanistic and functional studies of complement, and as an efficient inhibitor of complement under conditions of excessive CP activation.

PubMed: 32849513
DOI: 10.3389/fimmu.2020.01504

実験手法

X-RAY DIFFRACTION (2.19 Å)