9HY5

sc-4E (scFv derived from the mAb 4E1 against CD93) crystallized at pH 9.0

9HY5 の概要

• エントリーDOI: 10.2210/pdb9hy5/pdb
• 関連するPDBエントリー: 9HY1 9HY2 9HY3
• 分子名称: sc-4E (scFv derived from the mAb 4E1 against CD93), CHLORIDE ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: single-chain antibody fragment, scfv, monoclonal antibody 4e1 against cd93, sc-4e, immune system
• 由来する生物種: Mus musculus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29366.48

構造登録者

Raucci, L.,Orlandini, M.,Pozzi, C. (登録日: 2025-01-09, 公開日: 2025-04-30)

主引用文献

Raucci, L.,Perrone, C.D.,Barbera, S.,de Boer, L.J.,Tosi, G.M.,Brunetti, J.,Bracci, L.,Pozzi, C.,Galvagni, F.,Orlandini, M.
Structural and antigen-binding surface definition of an anti-CD93 monoclonal antibody for the treatment of degenerative vascular eye diseases.
Int.J.Biol.Macromol., 309:143118-143118, 2025

PubMed Abstract: CD93 is a receptor predominantly expressed on the surface of endothelial cells, where it plays a pivotal role in angiogenesis through its interaction with the extracellular matrix. In our previous studies, we identified the monoclonal antibody 4E1 as a potent inhibitor of angiogenesis by targeting the CD93-Multimerin-2 axis. Here, we report the development of 4E1 as a recombinant whole immunoglobulin and a single-chain variable fragment, designated sc-4E. Both formats retained the binding properties of the parental monoclonal antibody and exhibited comparable inhibitory effects on endothelial cell migration and differentiation. To elucidate the molecular basis of the 4E1-CD93 interaction, we initially employed machine learning-based modeling and docking analyses of the variable heavy and light domains of 4E1. Subsequent crystallographic analysis of sc-4E provided high-resolution structural insights, confirming and validating the predicted model. Further docking experiments and molecular dynamics simulations using the crystallographic structures of CD93 and sc-4E revealed that the interaction is primarily mediated by the CDR-H3 and CDR-L2 loops. Notably, these regions engage with the sushi-like domain of CD93, which is critical for its interaction with Multimerin-2. This comprehensive structural and functional characterization of 4E1 and sc-4E underscores their potential as anti-angiogenic agents. By effectively inhibiting endothelial cell migration and differentiation, 4E1 derivatives represent promising therapeutic candidates for the treatment of ocular vascular diseases driven by pathological angiogenesis.

PubMed: 40228767
DOI: 10.1016/j.ijbiomac.2025.143118

実験手法

X-RAY DIFFRACTION (1.6 Å)