2z8v
From Proteopedia
|
Structure of an IgNAR-AMA1 complex
Overview
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.
About this Structure
2Z8V is a Protein complex structure of sequences from Orectolobus maculatus and Plasmodium falciparum 3d7. Full crystallographic information is available from OCA.
Reference
Structure of an IgNAR-AMA1 Complex: Targeting a Conserved Hydrophobic Cleft Broadens Malarial Strain Recognition., Henderson KA, Streltsov VA, Coley AM, Dolezal O, Hudson PJ, Batchelor AH, Gupta A, Bai T, Murphy VJ, Anders RF, Foley M, Nuttall SD, Structure. 2007 Nov;15(11):1452-66. PMID:17997971
Page seeded by OCA on Wed Jan 23 12:00:30 2008
