7ZOZ

Crystal structure of Siglec-15 in complex with Fab

7ZOZ の概要

• エントリーDOI: 10.2210/pdb7zoz/pdb
• 分子名称: Sialic acid-binding Ig-like lectin 15, Anti-Siglec 15 Fab HC, Anti-Siglec 15 Fab LC, ... (4 entities in total)
• 機能のキーワード: sialic acid, siglec, immune system, cancer
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 81742.60

構造登録者

Lenza, M.P.,Oyenarte, I.,Jimenez-Barbero, J.,Ereno-Orbea, J. (登録日: 2022-04-26, 公開日: 2023-06-28, 最終更新日: 2024-02-07)

主引用文献

Lenza, M.P.,Egia-Mendikute, L.,Antonana-Vildosola, A.,Soares, C.O.,Coelho, H.,Corzana, F.,Bosch, A.,Manisha, P.,Quintana, J.I.,Oyenarte, I.,Unione, L.,Moure, M.J.,Azkargorta, M.,Atxabal, U.,Sobczak, K.,Elortza, F.,Sutherland, J.D.,Barrio, R.,Marcelo, F.,Jimenez-Barbero, J.,Palazon, A.,Ereno-Orbea, J.
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b.
Nat Commun, 14:3496-3496, 2023

PubMed Abstract: Sialic acid-binding Ig-like lectin 15 (Siglec-15) is an immune modulator and emerging cancer immunotherapy target. However, limited understanding of its structure and mechanism of action restrains the development of drug candidates that unleash its full therapeutic potential. In this study, we elucidate the crystal structure of Siglec-15 and its binding epitope via co-crystallization with an anti-Siglec-15 blocking antibody. Using saturation transfer-difference nuclear magnetic resonance (STD-NMR) spectroscopy and molecular dynamics simulations, we reveal Siglec-15 binding mode to α(2,3)- and α(2,6)-linked sialic acids and the cancer-associated sialyl-Tn (STn) glycoform. We demonstrate that binding of Siglec-15 to T cells, which lack STn expression, depends on the presence of α(2,3)- and α(2,6)-linked sialoglycans. Furthermore, we identify the leukocyte integrin CD11b as a Siglec-15 binding partner on human T cells. Collectively, our findings provide an integrated understanding of the structural features of Siglec-15 and emphasize glycosylation as a crucial factor in controlling T cell responses.

PubMed: 37311743
DOI: 10.1038/s41467-023-39119-8

実験手法

X-RAY DIFFRACTION (2.104 Å)