A host-targeting signal in virulence proteins reveals a secretome in malarial infection.
Malaria parasites secrete proteins across the vacuolar membrane into the erythrocyte, inducing modifications linked to disease and parasite survival. We identified an 11-amino acid signal required for the secretion of proteins from the Plasmodium falciparum vacuole to the human erythrocyte. Bioinformatics predicted a secretome of >320 proteins and conservation of the signal across parasite species. Functional studies indicated the predictive value of the signal and its role in targeting virulence proteins to the erythrocyte and implicated its recognition by a receptor/transporter. Erythrocyte modification by the parasite may involve plasmodial heat shock proteins and be vastly more complex than hitherto realized.
Hiller
N Luisa
NL
Departments of Pathology and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Bhattacharjee
Souvik
S
van Ooij
Christiaan
C
Liolios
Konstantinos
K
Harrison
Travis
T
Lopez-Estraño
Carlos
C
Haldar
Kasturi
K
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D003600:Cytosol / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D017125:Genes, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D019076:Transgenes; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; C085731:erythrocyte membrane protein 1, Plasmodium falciparum