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Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes.

Chen L, Xu Y, Healer J, Thompson JK, Smith BJ, Lawrence MC, Cowman AF - Elife (2014)

View Article: PubMed Central - PubMed

Affiliation: Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

ABSTRACT

Plasmodium falciparum causes the most severe form of malaria in humans and is responsible for over 700,000 deaths annually. It is an obligate intracellular parasite and invades erythrocytes where it grows in a relatively protected niche. Invasion of erythrocytes is essential for parasite survival and this involves interplay of multiple protein–protein interactions. One of the most important interactions is binding of parasite invasion ligand families EBLs and PfRhs to host receptors on the surface of erythrocytes. PfRh5 is the only essential invasion ligand within the PfRh family and is an important vaccine candidate. PfRh5 binds the host receptor basigin. In this study, we have determined the crystal structure of PfRh5 using diffraction data to 2.18 Å resolution. PfRh5 exhibits a novel fold, comprising nine mostly anti-parallel α-helices encasing an N-terminal β-hairpin, with the overall shape being an elliptical disk. This is the first three-dimensional structure determined for the PfRh family of proteins.

Doi:: http://dx.doi.org/10.7554/eLife.04187.001

No MeSH data available.


Binding of mutant PfRh5 to basigin.(A) The binding affinity of the reduced and alkylated PfRh5 to basigin measured by SPR. (B) The binding affinity of the PfRh5 mutant, in which the disordered loop has been deleted, to basigin measured by SPR.DOI:http://dx.doi.org/10.7554/eLife.04187.012
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fig3: Binding of mutant PfRh5 to basigin.(A) The binding affinity of the reduced and alkylated PfRh5 to basigin measured by SPR. (B) The binding affinity of the PfRh5 mutant, in which the disordered loop has been deleted, to basigin measured by SPR.DOI:http://dx.doi.org/10.7554/eLife.04187.012

Mentions: To explore the structure–function relationship of PfRh5, we examined the relevance of the disulphide bonds and cysteine residues for the function of PfRh5 by reducing and alkylating PfRh5-C followed by measuring the binding affinity of the modified protein to basigin using surface plasmon resonance (Figure 3A). The reduced and alkylated PfRh5-C has an affinity for basigin with KD = 127 nM. A threefold reduction in affinity as compared to untreated PfRh5-C (KD = 43.4 nM) was consistent with the two disulphide-bonds being important for the stability of the overall fold of the protein rather than being directly involved in basigin binding.10.7554/eLife.04187.012Figure 3.Binding of mutant PfRh5 to basigin.


Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes.

Chen L, Xu Y, Healer J, Thompson JK, Smith BJ, Lawrence MC, Cowman AF - Elife (2014)

Binding of mutant PfRh5 to basigin.(A) The binding affinity of the reduced and alkylated PfRh5 to basigin measured by SPR. (B) The binding affinity of the PfRh5 mutant, in which the disordered loop has been deleted, to basigin measured by SPR.DOI:http://dx.doi.org/10.7554/eLife.04187.012
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356141&req=5

fig3: Binding of mutant PfRh5 to basigin.(A) The binding affinity of the reduced and alkylated PfRh5 to basigin measured by SPR. (B) The binding affinity of the PfRh5 mutant, in which the disordered loop has been deleted, to basigin measured by SPR.DOI:http://dx.doi.org/10.7554/eLife.04187.012
Mentions: To explore the structure–function relationship of PfRh5, we examined the relevance of the disulphide bonds and cysteine residues for the function of PfRh5 by reducing and alkylating PfRh5-C followed by measuring the binding affinity of the modified protein to basigin using surface plasmon resonance (Figure 3A). The reduced and alkylated PfRh5-C has an affinity for basigin with KD = 127 nM. A threefold reduction in affinity as compared to untreated PfRh5-C (KD = 43.4 nM) was consistent with the two disulphide-bonds being important for the stability of the overall fold of the protein rather than being directly involved in basigin binding.10.7554/eLife.04187.012Figure 3.Binding of mutant PfRh5 to basigin.

View Article: PubMed Central - PubMed

Affiliation: Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

ABSTRACT

Plasmodium falciparum causes the most severe form of malaria in humans and is responsible for over 700,000 deaths annually. It is an obligate intracellular parasite and invades erythrocytes where it grows in a relatively protected niche. Invasion of erythrocytes is essential for parasite survival and this involves interplay of multiple protein–protein interactions. One of the most important interactions is binding of parasite invasion ligand families EBLs and PfRhs to host receptors on the surface of erythrocytes. PfRh5 is the only essential invasion ligand within the PfRh family and is an important vaccine candidate. PfRh5 binds the host receptor basigin. In this study, we have determined the crystal structure of PfRh5 using diffraction data to 2.18 Å resolution. PfRh5 exhibits a novel fold, comprising nine mostly anti-parallel α-helices encasing an N-terminal β-hairpin, with the overall shape being an elliptical disk. This is the first three-dimensional structure determined for the PfRh family of proteins.

Doi:: http://dx.doi.org/10.7554/eLife.04187.001

No MeSH data available.