Tuesday, March 23, 2010

Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii

J Biol Chem. 2010 Mar 19. [Epub ahead of print]

Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii

Crawford J, Tonkin ML, Grujic O, Boulanger MJ.

University of Victoria, Canada.

Apical membrane antigen 1 (AMA1) is an essential component of the moving junction (MJ) complex used by apicomplexan parasites to invade host cells. We report the 2.0 A resolution X-ray crystal structure of the full ectodomain (domains I, II and III) of AMA1 from the pervasive protozoan parasite Toxoplasma gondii. The structure of T. gondii AMA1 (TgAMA1) is the most complete of any AMA1 structure to date with more than 97.5% of the ectodomain unambiguously modeled. Comparative sequence analysis reveals discrete segments in TgAMA1 that map to areas of established functional importance in AMA1 from Plasmodium vivax (PvAMA1) and falciparum (PfAMA1). Inspection of the TgAMA1 structure reveals a network of apical surface loops, reorganized in both size and chemistry relative to Pv/PfAMA1, that appear to serve as structural filters restricting access to a central hydrophobic groove. The terminal portion of this groove is formed by an extended loop from DII that is fourteen residues shorter in TgAMA1. A pair of tryptophan residues (Trp353 and Trp354) anchor the DII loop in the hydrophobic groove and frame a conserved tyrosine (Tyr230) forming a contiguous surface that may be critical for MJ assembly. The minimalist DIII structure folds into a cystine knot that likely stabilizes and orients the bulk of the ectodmain without providing excess surface area to which invasion inhibitory antibodies can be generated. The detailed structural characterization of TgAMA1 provides valuable insight into the mechanism of host cell invasion by T. gondii.

PMID: 20304917 [PubMed - as supplied by publisher]

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