1hn6
From Proteopedia
|
SOLUTION STRUCTURE OF PLASMODIUM FALCIPARUM APICAL MEMBRANE ANTIGEN 1 (RESIDUES 436-545)
Overview
Apical membrane antigen 1 of the malarial parasite Plasmodium falciparum, (Pf AMA1) is a merozoite antigen that is considered a strong candidate for, inclusion in a malaria vaccine. Antibodies reacting with disulphide, bond-dependent epitopes in AMA1 block invasion of host erythrocytes by, P.falciparum merozoites, and we show here that epitopes involving sites of, mutations in domain III are targets of inhibitory human antibodies. The, solution structure of AMA1 domain III, a 14kDa protein, has been, determined using NMR spectroscopy on uniformly 15N and 13C/15N-labelled, samples. The structure has a well-defined disulphide-stabilised core, region separated by a disordered loop, and both the N and C-terminal, regions of the molecule are unstructured. Within the disulphide-stabilised, core, residues 443-447 form a turn of helix and residues 495-498 and, 503-506 an anti-parallel beta-sheet with a distorted type I beta-turn, centred on residues 500-501, producing a beta-hairpin-type structure. The, structured region of the molecule includes all three disulphide bonds. The, previously unassigned connectivities for two of these bonds could not be, established with certainty from the NMR data and structure calculations, but were determined to be C490-C507 and C492-C509 from an antigenic, analysis of mutated forms of this domain expressed using phage display., Naturally occurring mutations in domain III that are located far apart in, the primary sequence tend to cluster in the region of the disulphide core, in the three-dimensional structure of the molecule. The structure shows, that nearly all the polymorphic sites have a high level of solvent, accessibility, consistent with their location in epitopes recognised by, protective antibodies. Even though domain III in solution contains, significant regions of disorder in the structure, the, disulphide-stabilised core that is structured is clearly an important, element of the antigenic surface of AMA1 recognised by protective, antibodies.
About this Structure
1HN6 is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.
Reference
Structure of domain III of the blood-stage malaria vaccine candidate, Plasmodium falciparum apical membrane antigen 1 (AMA1)., Nair M, Hinds MG, Coley AM, Hodder AN, Foley M, Anders RF, Norton RS, J Mol Biol. 2002 Sep 27;322(4):741-53. PMID:12270711
Page seeded by OCA on Sun Nov 25 02:48:16 2007
