4GOS

Crystal structure of human B7-H4 IgV-like domain

Summary for 4GOS

• Entry DOI: 10.2210/pdb4gos/pdb
• Descriptor: 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)
• Functional Keywords: 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
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 14633.26

Authors

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) (deposition date: 2012-08-20, release date: 2012-09-12, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.59 Å)