2j4w

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Revision as of 07:44, 18 November 2007

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spinqualitylabelsall models 2j4w, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF A PLASMODIUM VIVAX APICAL MEMBRANE ANTIGEN 1-FAB F8.12.19 COMPLEX

Overview

Apical membrane antigen 1 (AMA1) has an important, but as yet, uncharacterised, role in host cell invasion by the malaria parasite, Plasmodium. The protein, which is quite conserved between Plasmodium, species, comprises an ectoplasmic region, a single transmembrane segment, and a small cytoplasmic domain. The ectoplasmic region, which can induce, protective immunity in animal models of human malaria, is a leading, vaccine candidate that has entered clinical trials. The monoclonal, antibody F8.12.19, raised against the recombinant ectoplasmic region of, AMA1 from Plasmodium vivax, cross-reacts with homologues from Plasmodium, knowlesi, Plasmodium cynomolgi, Plasmodium berghei and Plasmodium, falciparum, as shown by immunofluorescence assays on mature schizonts. The, binding of F8.12.19 to recombinant AMA1 from both P. vivax and P., falciparum was measured by surface plasmon resonance, revealing an, apparent affinity constant that is about 100-fold weaker for the, cross-reacting antigen when compared to the cognate antigen. Crystal, structure analysis of Fab F8.12.19 complexed to AMA1 from P. vivax and P., falciparum shows that the monoclonal antibody recognises a discontinuous, epitope located on domain III of the ectoplasmic region, the major, component being a loop containing a cystine knot. The structures provide a, basis for understanding the cross-reactivity. Antibody contacts are made, mainly to main-chain and invariant side-chain atoms of AMA1; contact, antigen residues that differ in sequence are located at the periphery of, the antigen-binding site and can be accommodated at the interface between, the two components of the complex. The implications for AMA1 vaccine, development are discussed.

About this Structure

2J4W is a Protein complex structure of sequences from Mus musculus and Plasmodium vivax. Full crystallographic information is available from OCA.

Reference

Cross-reactivity studies of an anti-Plasmodium vivax apical membrane antigen 1 monoclonal antibody: binding and structural characterisation., Igonet S, Vulliez-Le Normand B, Faure G, Riottot MM, Kocken CH, Thomas AW, Bentley GA, J Mol Biol. 2007 Mar 9;366(5):1523-37. Epub 2006 Dec 16. PMID:17229439

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