Molecular variation in a novel polymorphic antigen associated with Plasmodium falciparum merozoites

Damian J. McColl, Anabel Silva, Michael Foley, Jürgen F J Kun, Jennifer M. Favaloro, Jennifer K. Thompson, Vikki M. Marshall, Ross L. Coppel, David J. Kemp, Robin F. Anders

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Abstract

A cDNA clone encoding part of a novel polymorphic merozoite antigen from Plasmodium falciparum was isolated by screening a cDNA library with human immune serum from Papua New guinea. Immunofluoresence microscopy and immunoblotting with affinity-purified antibodies recognized a highly polymorphic antigen, Ag956, present in schizonts and merozoites. Biosynthetic labeling and immunoprecipitation experiments demonstrated that Ag956 is proteolytically cleaved during merozoite maturation. The complete genomic sequence of Ag956 from the D10 clone of P. falciparum isolate FC27 encodes a secreted protein of calculated molecular mass 43 243 that is very hydrophilic and contains a region of unusual heptad repeats of the general structure AXXAXXX. This antigen has been named the secreted polymorphic antigen associated with merozoites (SPAM). The sequence of a second SPAM allele from the 3D7 clone of isolate NF54 reveals that the alanine heptad repeats and the hydrophilic C-terminal half of the protein are conserved. Variation among SPAM alleles is the result of deletion and amino acid substitutions in non-repetitive sequences within and flanking the alanine heptad-repeat domain. Heptad repeats in which the a and d position contain hydrophobic residues generate amphipathic α-helices which give rise to helical bundles or coiled-coil structures in proteins. Thus, SPAM is the first example of a P. falciparum antigen in which a repetitive sequence has features characteristics of a well-defined structural element.

Original languageEnglish
Pages (from-to)53-67
Number of pages15
JournalMolecular and Biochemical Parasitology
Volume68
Issue number1
DOIs
Publication statusPublished - 1 Jan 1994
Externally publishedYes

Keywords

  • Alanine heptad repeat
  • Merozoite
  • Plasmodium falciparum
  • Polymorphism
  • Proteolytic processing
  • Secreted polymorphic antigen associated with merozoites (SPAM)

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