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Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28

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Abstract

The structure of human CTLA-4 reveals that residues Met 99, Tyr 100 and Tyr 104 of the M99 YPPPY104 motif are adjacent to a patch of charged surface residues on the A‘GFCC’ face of the protein. Mutation of these residues, which are conserved in the CTLA-4/CD28 family, significantly reduces binding to CD80 and/or CD86, implicating this patch as a ligand binding site.

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Authors and Affiliations

  1. Departments of Macromolecular NMR, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, New Jersey, 08543-4000, USA

    William J. Metzler, Keith L. Constantine & Luciano Mueller

  2. Peptide and Protein Research, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, New Jersey, 08543-4000, USA

    William Fenderson, Shyh-Yu Shaw & Thomas B. Lavoie

  3. Departments of Inflammation, Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Avenue, Seattle, Washington, 98121, USA

    Jürgen Bajorath

  4. Immunomodulation, Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Avenue, Seattle, Washington, 98121, USA

    Joseph Naemura, Gina Leytze, Robert J. Peach & Peter S. Linsley

Authors
  1. William J. Metzler
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  2. Jürgen Bajorath
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  3. William Fenderson
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  4. Shyh-Yu Shaw
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  5. Keith L. Constantine
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  6. Joseph Naemura
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  7. Gina Leytze
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  8. Robert J. Peach
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  9. Thomas B. Lavoie
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  10. Luciano Mueller
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  11. Peter S. Linsley
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Correspondence to William J. Metzler.

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Metzler, W., Bajorath, J., Fenderson, W. et al. Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28. Nat Struct Mol Biol 4, 527–531 (1997). https://doi.org/10.1038/nsb0797-527

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  • DOI: https://doi.org/10.1038/nsb0797-527

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