4GOS

Crystal structure of human B7-H4 IgV-like domain

4GOS の概要

• エントリーDOI: 10.2210/pdb4gos/pdb
• 分子名称: V-set domain-containing T-cell activation inhibitor 1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: immunoglobulin domain, glycoprotein, disulfide bond, immunity, adaptive immunity, structural genomics, psi-biology, protein structure initiative, new york structural genomics research consortium, nysgrc, immunoglobulin variable-like domain, cell surface, immune system, atoms-to-animals: the immune function network, ifn
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14633.26

構造登録者

Vigdorovich, V.,Ramagopal, U.,Bhosle, R.,Toro, R.,Nathenson, S.G.,Almo, S.C.,New York Structural Genomics Research Consortium (NYSGRC),Atoms-to-Animals: The Immune Function Network (IFN) (登録日: 2012-08-20, 公開日: 2012-09-12, 最終更新日: 2024-11-06)

主引用文献

Jeon, H.,Vigdorovich, V.,Garrett-Thomson, S.C.,Janakiram, M.,Ramagopal, U.A.,Abadi, Y.M.,Lee, J.S.,Scandiuzzi, L.,Ohaegbulam, K.C.,Chinai, J.M.,Zhao, R.,Yao, Y.,Mao, Y.,Sparano, J.A.,Almo, S.C.,Zang, X.
Structure and cancer immunotherapy of the B7 family member B7x.
Cell Rep, 9:1089-1098, 2014

PubMed Abstract: B7x (B7-H4 or B7S1) is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but it is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest that it may be a potent immunosuppressive pathway in human cancers. Here, we determined the crystal structure of the human B7x immunoglobulin variable (IgV) domain at 1.59 Å resolution and mapped the epitopes recognized by monoclonal antibodies. We developed an in vivo system to screen therapeutic monoclonal antibodies against B7x and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor rechallenge. Our data suggest that targeting B7x on tumors is a promising cancer immunotherapy and humanized 1H3 may be efficacious for immunotherapy of human cancers.

PubMed: 25437562
DOI: 10.1016/j.celrep.2014.09.053

実験手法

X-RAY DIFFRACTION (1.59 Å)