1JBF

Hairpin Peptide that Inhibits IgE Activity by Binding to the High Affinity IgE Receptor

Summary for 1JBF

• Entry DOI: 10.2210/pdb1jbf/pdb
• Descriptor: IGE06 (1 entity in total)
• Functional Keywords: beta-hairpin, type i turn, protein binding
• Total number of polymer chains: 1
• Total formula weight: 1776.09

Authors

Nakamura, G.R.,Starovasnik, M.A.,Reynolds, M.E.,Lowman, H.B. (deposition date: 2001-06-04, release date: 2001-08-22, Last modification date: 2024-11-20)

Primary citation

Nakamura, G.R.,Starovasnik, M.A.,Reynolds, M.E.,Lowman, H.B.
A novel family of hairpin peptides that inhibit IgE activity by binding to the high-affinity IgE receptor.
Biochemistry, 40:9828-9835, 2001

PubMed Abstract: A family of structured peptides that bind to FcepsilonRIalpha, the alpha-chain of the high-affinity receptor for IgE, has been identified. Binding selections using FcepsilonRIalpha and polyvalent peptide-phage libraries yielded a dominant 18-residue peptide-phage clone, as well as related sequences that did not resemble fragments of IgE. Synthetic peptides based on these sequences inhibited IgE binding to its receptor, and were found by NMR analysis to adopt a stable beta-hairpin structure in solution. Optimized peptides with micromolar receptor affinity exhibited high stability in biological fluids and inhibited cellular histamine release in an in vitro bioassay of IgE activity. The structure-activity relationships of these peptides, which are less than 1% of the size of IgE, suggest an overlap between their binding site and that of IgE on FcepsilonRI. Thus, the peptides demonstrate that blocking a small epitope on this receptor chain is sufficient to block IgE activity. Such structured peptides represent a possible starting point for the design of novel antagonists, and offer the potential for testing in vivo a new approach for treating allergic disease.

PubMed: 11502176
DOI: 10.1021/bi0109360

Experimental method

SOLUTION NMR