2j4w: Difference between revisions

Revision as of 08:20, 4 May 2008

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

OverviewOverview

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 StructureAbout this Structure

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

ReferenceReference

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 Page seeded by OCA on Sun May 4 08:20:12 2008

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OCA

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 [[Image:2j4w.gif|left|200px]]
- {{Structure
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 '''STRUCTURE OF A PLASMODIUM VIVAX APICAL MEMBRANE ANTIGEN 1-FAB F8.12.19 COMPLEX'''
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 [[Category: Riottot, M M.]]
 [[Category: Thomas, A W.]]
-[[Category: antibody cross-reactivity]]
+[[Category: Antibody cross-reactivity]]
-[[Category: apical membrane antigen 1]]
+[[Category: Apical membrane antigen 1]]
-[[Category: hypothetical protein]]
+[[Category: Hypothetical protein]]
-[[Category: immune system]]
+[[Category: Immune system]]
-[[Category: immunoglobulin c region]]
+[[Category: Immunoglobulin c region]]
-[[Category: immunoglobulin domain]]
+[[Category: Immunoglobulin domain]]
-[[Category: malaria vaccine candidate]]
+[[Category: Malaria vaccine candidate]]
-[[Category: membrane]]
+[[Category: Membrane]]
-[[Category: surface active protein]]
+[[Category: Surface active protein]]
-[[Category: transmembrane]]
+[[Category: Transmembrane]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 08:20:12 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:52:57 2008''