5VL3

CD22 d1-d3 in complex with therapeutic Fab Epratuzumab

5VL3 の概要

• エントリーDOI: 10.2210/pdb5vl3/pdb
• 関連するPDBエントリー: 5VKJ 5VKK 5VKM
• EMDBエントリー: 8704 8705
• 分子名称: B-cell receptor CD22, Epratuzumab Fab Heavy Chain, Epratuzumab Fab Light Chain, ... (8 entities in total)
• 機能のキーワード: therapeutic antibody, siglec, b cell, fab, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 345472.70

構造登録者

Sicard, T.,Ereno-Orbea, J.,Julien, J.P. (登録日: 2017-04-24, 公開日: 2017-10-11, 最終更新日: 2020-07-29)

主引用文献

Ereno-Orbea, J.,Sicard, T.,Cui, H.,Mazhab-Jafari, M.T.,Benlekbir, S.,Guarne, A.,Rubinstein, J.L.,Julien, J.P.
Molecular basis of human CD22 function and therapeutic targeting.
Nat Commun, 8:764-764, 2017

PubMed Abstract: CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers. Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins. The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals. We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement. Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells. Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.

PubMed: 28970495
DOI: 10.1038/s41467-017-00836-6

実験手法

X-RAY DIFFRACTION (3.1 Å)