TY - JOUR
T1 - Structure and t cell inhibition properties of b7 family member, B7-H3
AU - Vigdorovich, Vladimir
AU - Ramagopal, Udupi A.
AU - Lázár-Molnár, Eszter
AU - Sylvestre, Eliezer
AU - Lee, Jun Sik
AU - Hofmeyer, Kimberly A.
AU - Zang, Xingxing
AU - Nathenson, Stanley G.
AU - Almo, Steven C.
N1 - Funding Information:
The authors gratefully acknowledge Dr. Jeffrey B. Bonanno for helpful discussions during structure determination, Dr. Kaya Ghosh for her contributions to the T cell-based assay setup, Dr. Deborah Palliser for her help with the experimental design, and Dr. Teresa P. DiLorenzo for her insightful suggestions during the writing of this manuscript. This work was supported in part by NIH grants GM094662 (to S.C.A.), GM094665 (to S.G.N.), AI007289 (to S.G.N. and S.C.A.), DP2DK083076 (to X.Z.), and CA009173 and the Irvington Institute Fellowship Program of the Cancer Research Institute (to V.V.), and Department of Defense Grant PC094137 (to X.Z.). The Albert Einstein Cancer Center is supported by NIH P30CA013330.
PY - 2013/5/7
Y1 - 2013/5/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.str.2013.03.003
DO - 10.1016/j.str.2013.03.003
M3 - Article
C2 - 23583036
AN - SCOPUS:84877577461
SN - 0969-2126
VL - 21
SP - 707
EP - 717
JO - Structure
JF - Structure
IS - 5
ER -
