Additional remarks phenotype | Mutant/mutation
The mutant expresses a mutated form of Pyebl with an amino acid substitution (Tyr >Cys) at position 351(17x1.1pp-EBL-351Y>C)
Protein (function)
Pyebl is a gene encoding a type I integral transmembrane protein encoded by the ebl (erythrocyte-binding-like) gene family. Upon release from the micronemes, EBL proteins recognize erythrocyte receptors and initiate the formation of the tight junction. Plasmodium vivax uses an EBL orthologue, PvDBP (Pv110810), to recognize the Duffy antigen on the erythrocyte surface. P. falciparum has an expanded family of EBL proteins, for example EBA175 (PF07_0128), EBA181/JESEBL (PFA0125c), EBA140/BAEBL (MAL13P1.60), EBL1 (PFD1145c).
EBL proteins possess 2 Cys-rich regions conserved among EBL orthologues. The N-terminal Cys-rich region named the DBL (Duffy-binding-like) domain or region 2 recognizes a specific erythrocyte surface receptor. The C-terminal Cys-rich region named the C-cys domain or region 6 is located adjacent to the transmembrane domain, and the number and location of Cys residues are well conserved among Plasmodium species. Region 6 exhibits structural similarity to the KIX-binding domain of the coactivator CREB-binding protein and has been proposed to be a protein trafficking signal for transportation to the micronemes.
Phenotype
Reduced growth rate of blood stages of the mutant (17x1.1pp-EBL-351Y>C) compared to wild type (17x1.1pp)
Additional information
Examining the Pyebl gene, Sanger capillary sequencing re-confirmed the existence in 17X1.1pp of an amino acid substitution (Cys >Tyr) at position 351 within region 2 of the encoded protein. When aligned against other P. yoelii strains and other Plasmodium species, this cysteine residue is highly conserved, and the substitution observed in 17X1.1pp was novel. Crucially, no other polymorphisms were detected in the coding sequence of the gene, including in region 6, the location of the SNP previously implicated in parasite virulence in other strains of P. yoelii.
Structural modeling of the EBL protein in both wild-type and 17x1.1pp (C351Y) mutants predicted the abolition of a a disulphide bond between C351 and C420 in the 17x1.1pp parasites that alters the tertiary structure of the receptor binding region of the ligand in these parasites.
Other mutants
see PY17X_1337400 |