Structure and t cell inhibition properties of b7 family member, B7-H3

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

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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.

Original languageEnglish (US)
Pages (from-to)707-717
Number of pages11
JournalStructure
Volume21
Issue number5
DOIs
StatePublished - May 7 2013

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ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Vigdorovich, V., Ramagopal, U. A., Lázár-Molnár, E., Sylvestre, E., Lee, J. S., Hofmeyer, K. A., Zang, X., Nathenson, S. G., & Almo, S. C. (2013). Structure and t cell inhibition properties of b7 family member, B7-H3. Structure, 21(5), 707-717. https://doi.org/10.1016/j.str.2013.03.003