Phage-displayed peptides bind to the malarial protein apical membrane antigen-1 and inhibit the merozoite invasion of host erythrocytes.
Apical membrane antigen-1 (AMA1) is a transmembrane protein present on the surface of merozoites that is thought to be involved in the process of parasite invasion of host erythrocytes. Although it is the target of a natural immune response that can inhibit invasion, little is known about the molecular mechanisms by which AMA1 facilitates the invasion process. In an attempt to identify peptides that specifically interact with and block the function of AMA1, a random peptide library displayed on the surface of filamentous phage was panned on recombinant AMA1 from Plasmodium falciparum. Three peptides with affinity for AMA1 were isolated, and characterization of their fine binding specificities indicated that they bind to a similar region on the surface of AMA1. One of these peptides was found to be a potent inhibitor of the invasion of P. falciparum merozoites into human erythrocytes. We propose that this peptide blocks interaction between AMA1 and a ligand on the erythrocyte surface that is involved in a critical step in malarial invasion. The identification and characterization of these peptide inhibitors now permit an evaluation of the essential requirements that are necessary for efficient neutralization of merozoite invasion by blocking AMA1 function.
Li
Felomena
F
Department of Biochemistry, La Trobe University, Bundoora, 3083 Victoria, Australia.
Dluzewski
Anton
A
Coley
Andrew M
AM
Thomas
Alan
A
Tilley
Leann
L
Anders
Robin F
RF
Foley
Michael
M
D000409:Alanine; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000494:pharmacology*; D019151:Peptide Library; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D000953:Antigens, Protozoan; D008565:Membrane Proteins; D010446:Peptide Fragments; D019151:Peptide Library; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C090077:apical membrane antigen I, Plasmodium; D000409:Alanine