2MUA

Shifting the Polarity of some Critical Residues in Malarial Peptides Binding to Host Cells is a Key Factor in Breaking Conserved Antigens

2MUA の概要

• エントリーDOI: 10.2210/pdb2mua/pdb
• NMR情報: BMRB: 25204
• 分子名称: Ring-infected erythrocyte surface antigen (1 entity in total)
• 機能のキーワード: immune system
• 由来する生物種: Plasmodium falciparum
• 細胞内の位置: Cell membrane; Peripheral membrane protein; Cytoplasmic side: P13830
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2457.89

構造登録者

Cifuentes, G.,Bermudez, A.,Rodriguez, R.,Patarroyo, M. (登録日: 2014-09-05, 公開日: 2015-09-16, 最終更新日: 2024-05-01)

主引用文献

Cifuentes, G.,Bermudez, A.,Rodriguez, R.,Patarroyo, M.A.,Patarroyo, M.E.
Shifting the polarity of some critical residues in malarial peptides' binding to host cells is a key factor in breaking conserved antigens' code of silence.
MEDICINAL CHEMISTRY, 4:278-292, 2008

PubMed Abstract: As microbes use many mechanisms for avoiding immunological pressure, new strategies must be developed to bypass the immunological code of silence of conserved, functionally-important amino acid sequences, such as those involved in high activity binding peptides' (HABPs) attaching to their host cells. Hundreds of experiments in large numbers of Aotus monkeys revealed that this immunological code of silence could be broken by shifting the polarity of some critical host cell binding residues in these HABPs by substituting F for R and vice versa, Y<-->W, L<-->H, I<-->N, P<-->D, M<-->K or E, C<-->T, V<-->N or S; there are special rules for A, G and S. (1)H-nuclear magnetic resonance of these modified, immunogenic, protection-inducing HABPs and molecular modelling revealed that such modifications induced appropriate fitting into specific HLA-DRbeta1 Pockets, suggesting the presence of new pockets and a haplotype- and allele-specific conscious TCR. A highly immunogenic and protection-inducing anti-malarial vaccine can thus be produced.

PubMed: 18473921

実験手法

SOLUTION NMR