CD80 binding polyproline helical peptide inhibits T cell activation

Mythily Srinivasan, Debao Lu, Rajaraman Eri, David D. Brand, Azizul Haque, Janice Blum

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The critical role played by the CD28/CD152-CD80/ CD86 costimulatory molecules in mediating T cell activation and suppression provides attractive targets for therapeutic strategies. CD28 and CD152 share a conserved polyproline motif in the ligand-binding region. Similar proline-rich regions in globular domains preferentially adopt a polyproline type II (PPII) helical conformation and are involved in transient protein-protein interactions. Interestingly, in the human CD80-CD152 complex, Pro102 of CD152 restricts the preceding proline to PPII helix in the binding orientation in relation to the shallow binding pocket of CD80. Peptide agents derived from binding sites of receptors that mimic the bioactive conformation have been shown to block receptor-ligand interactions. Contact preferences of the interface amino acids at the protein-protein interaction sites and the propensity of each residue to form PPII helix were integrated in the design of novel peptide agents referred to as CD80 competitive antagonist peptides. Structural and functional studies suggest potential therapeutic value for select CD80 competitive antagonist peptides.

Original languageEnglish
Pages (from-to)10149-10155
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number11
DOIs
StatePublished - Mar 18 2005

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Peptide T
T-cells
Chemical activation
T-Lymphocytes
Peptides
Proline
Conformations
Proteins
Ligands
Binding Sites
Amino Acids
Molecules
polyproline
Therapeutics
CD80-CAP

ASJC Scopus subject areas

  • Biochemistry

Cite this

CD80 binding polyproline helical peptide inhibits T cell activation. / Srinivasan, Mythily; Lu, Debao; Eri, Rajaraman; Brand, David D.; Haque, Azizul; Blum, Janice.

In: Journal of Biological Chemistry, Vol. 280, No. 11, 18.03.2005, p. 10149-10155.

Research output: Contribution to journalArticle

Srinivasan, Mythily ; Lu, Debao ; Eri, Rajaraman ; Brand, David D. ; Haque, Azizul ; Blum, Janice. / CD80 binding polyproline helical peptide inhibits T cell activation. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 11. pp. 10149-10155.
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