1KCO

Structure of e131 Zeta Peptide, a Potent Antagonist of the High-Affinity IgE Receptor

1KCO の概要

• エントリーDOI: 10.2210/pdb1kco/pdb
• 関連するPDBエントリー: 1KCN
• 分子名称: e131 Zeta Peptide (1 entity in total)
• 機能のキーワード: disulfide-bonded, helical, "zeta" structure, protein binding
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2537.91

構造登録者

Nakamura, G.R.,Reynolds, M.E.,Chen, Y.M.,Starovasnik, M.A.,Lowman, H.B. (登録日: 2001-11-09, 公開日: 2002-03-06, 最終更新日: 2024-11-13)

主引用文献

Nakamura, G.R.,Reynolds, M.E.,Chen, Y.M.,Starovasnik, M.A.,Lowman, H.B.
Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor.
Proc.Natl.Acad.Sci.USA, 99:1303-1308, 2002

PubMed Abstract: Recently we described a family of peptides, unrelated in sequence to IgE, that form stable beta-hairpins in solution and inhibit IgE activity in the microM range [Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E. & Lowman, H. B. (2001) Biochemistry 40, 9828-9835]. Using an expanded set of peptide-phage libraries, we found a simpler motif, X(2)CPX(2)CYX, for binding to the high-affinity IgE receptor. In solution, one of these peptides spontaneously formed a covalent antiparallel dimer. We subsequently linked these monomers in a single-chain construct on phage and optimized receptor binding. Ultimately, peptides with 30 nM affinity were produced. NMR studies showed that the peptide adopts a stable fold consisting of two "zeta" (zeta)-shaped moieties. Structure-activity analyses reveal a single binding site created by the zeta-dimer, with two tyrosine residues important for structural stability and two proline residues important for Fc epsilon RI binding. The peptides inhibit histamine release from cultured cells and are extremely stable in biological fluids. The zeta peptides appear to act as competitive IgE inhibitors and suggest possibilities for design of novel IgE antagonists.

PubMed: 11830661
DOI: 10.1073/pnas.022635599

実験手法

SOLUTION NMR