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PMID: 23583036 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Structure (London, England : 1993) ·Vol. 21 ·No. 5 ·2013-05-07 ·Pages 707-17

Vigdorovich V, Ramagopal UA, Lázár-Molnár E, Sylvestre E, Lee JS, Hofmeyer KA, Zang X, Nathenson SG, Almo SC

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals B7 Antigens/chemistry,metabolism Cells, Cultured Crystallography, X-Ray Drosophila Lymphocyte Activation Mice Models, Molecular Molecular Sequence Data Protein Conformation T-Lymphocytes/metabolism
Chemicals
B7 Antigens Cd276 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Vigdorovich Vladimir
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. vladimir.vigdorovich@gmail.com
Ramagopal Udupi A
Lázár-Molnár Eszter
Sylvestre Eliezer
Lee Jun Sik
Hofmeyer Kimberly A
Zang Xingxing
Nathenson Stanley G
Almo Steven C
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
1878-4186
DOI
10.1016/j.str.2013.03.003
Email
vladimir.vigdorovich@gmail.com
Published
2013-05-07
Epub
2013-00-11
Pages
707-17
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC3998375
Subset
IM
Grants
NCI NIH HHS · P30CA013330 · United States
NCI NIH HHS · CA009173 · United States
NCI NIH HHS · T32 CA009173 · United States
NIGMS NIH HHS · GM094665 · United States
NIGMS NIH HHS · GM094662 · United States
NIAID NIH HHS · R56 AI007289 · United States
NCI NIH HHS · P30 CA013330 · United States
NIGMS NIH HHS · U54 GM094662 · United States
NIDDK NIH HHS · DP2 DK083076 · United States
NIAID NIH HHS · AI007289 · United States
NIGMS NIH HHS · U01 GM094665 · United States
NIDDK NIH HHS · DP2DK083076 · United States
NIAID NIH HHS · R01 AI007289 · United States
External Links
PubMed source DOI: 10.1016/j.str.2013.03.003 PMC Full Text View journal details
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