Hyper-expansion of asparagines correlates with an abundance of proteins with prion-like domains in Plasmodium falciparum.
Plasmodium falciparum encodes approximately 5300 proteins of which approximately 35% have repeats of amino acids, significantly higher than in other fully sequenced eukaryotes. The proportion of proteins with amino acid homorepeats varies from 4 to 54% amongst different functional classes of proteins. These homorepeats are dominated by asparagines, which are selected over lysines despite equivalent AT codon content. Surprisingly, asparagine repeats are absent from the variant surface antigen protein families of PfEMP1s, Stevors and Rifins. The PfEMP1 protein family is instead rich in recurrences of glutamates, similar to human cell surface proteins. Structural mapping of homorepeats suggests that these segments are likely to form surface exposed structures that protrude from the main protein cores. We also found an abundance of asparagine-rich prion-like domains in P. falciparum, significantly larger than in any other eukaryote. Domains rich in glutamines and asparagines have an innate predisposition to form self-propagating amyloid fibers, which are involved both in prion-based inheritance and in human neurodegenerative disorders. Nearly 24% (1302 polypeptides) of P. falciparum proteins contain prion-forming or prion-inducing domains, in comparison to Drosophila (approximately 3.4%) which to date showed the highest number of prion-like proteins. The unexpected properties of P. falciparum revealed here open new avenues for investigating parasite biology.
Singh
Gajinder Pal
GP
Malaria Research Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
Chandra
Beeram Ravi
BR
Bhattacharya
Arindam
A
Akhouri
Reetesh Raj
RR
Singh
Saurabh Kumar
SK
Sharma
Amit
A
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics; D001216:Asparagine / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid
D000953:Antigens, Protozoan; D011328:Prions; D015800:Protozoan Proteins; C474556:STEVOR antigen, Plasmodium falciparum; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D001216:Asparagine