Structure and T cell inhibition properties of B7 family member, B7-H3.

Publication Type:

Journal Article

Authors:

Vigdorovich, Vladimir; Ramagopal, Udupi A; Lázár-Molnár, Eszter; Sylvestre, Eliezer; Lee, Jun Sik; Hofmeyer, Kimberly A; Zang, Xingxing; Nathenson, Stanley G; Almo, Steven C

Source:

Structure, Volume 21, Issue 5, p.707-17 (2013)

Keywords:

Amino Acid Sequence, Animals, B7 Antigens, Cells, Cultured, Crystallography, X-Ray, Drosophila, Lymphocyte Activation, Mice, Models, Molecular, Molecular Sequence Data, Protein Conformation, T-Lymphocytes

Abstract:

<p>T cell activity is controlled by a combination of antigen-dependent signaling through the T cell receptor and a set of auxiliary signals delivered through antigen-independent interactions, including the recognition of the B7 family of ligands. B7-H3 is a recently identified B7 family member that is strongly overexpressed in a range of cancers and correlates with poor prognosis. We report the crystal structure of murine B7-H3 at a 3 Å resolution, which provides a model for the organization of the IgV and IgC domains within the ectodomain. We demonstrate that B7-H3 inhibits T cell proliferation and show that the FG loop of the IgV domain plays a critical role in this function. B7-H3 crystallized as an unusual dimer arising from the exchange of the G strands in the IgV domains of partner molecules. This arrangement, in combination with previous reports, highlights the dynamic nature and plasticity of the immunoglobulin fold.</p>

Detector: 
Q315
Beamline: 
24-ID-E