2Z8V

Structure of an IgNAR-AMA1 complex

2Z8V の概要

• エントリーDOI: 10.2210/pdb2z8v/pdb
• 関連するPDBエントリー: 1VER 1Z40 2Z8W
• 分子名称: Apical membrane antigen 1, New antigen receptor variable domain (3 entities in total)
• 機能のキーワード: ama1-vnar complex, 14i-1, receptor, immune system
• 由来する生物種: Plasmodium falciparum; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 102342.76

構造登録者

Streltsov, V.A.,Henderson, K.A.,Batchelor, A.H.,Coley, A.M.,Nuttall, S.D. (登録日: 2007-09-11, 公開日: 2007-11-27, 最終更新日: 2024-11-06)

主引用文献

Henderson, K.A.,Streltsov, V.A.,Coley, A.M.,Dolezal, O.,Hudson, P.J.,Batchelor, A.H.,Gupta, A.,Bai, T.,Murphy, V.J.,Anders, R.F.,Foley, M.,Nuttall, S.D.
Structure of an IgNAR-AMA1 Complex: Targeting a Conserved Hydrophobic Cleft Broadens Malarial Strain Recognition
Structure, 15:1452-1466, 2007

PubMed Abstract: Apical membrane antigen 1 (AMA1) is essential for invasion of erythrocytes and hepatocytes by Plasmodium parasites and is a leading malarial vaccine candidate. Although conventional antibodies to AMA1 can prevent such invasion, extensive polymorphisms within surface-exposed loops may limit the ability of these AMA1-induced antibodies to protect against all parasite genotypes. Using an AMA1-specific IgNAR single-variable-domain antibody, we performed targeted mutagenesis and selection against AMA1 from three P. falciparum strains. We present cocrystal structures of two antibody-AMA1 complexes which reveal extended IgNAR CDR3 loops penetrating deep into a hydrophobic cleft on the antigen surface and contacting residues conserved across parasite species. Comparison of a series of affinity-enhancing mutations allowed dissection of their relative contributions to binding kinetics and correlation with inhibition of erythrocyte invasion. These findings provide insights into mechanisms of single-domain antibody binding, and may enable design of reagents targeting otherwise cryptic epitopes in pathogen antigens.

PubMed: 17997971
DOI: 10.1016/j.str.2007.09.011

実験手法

X-RAY DIFFRACTION (2.35 Å)