Limits...
The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors.

Chen Q, Heddini A, Barragan A, Fernandez V, Pearce SF, Wahlgren M - J. Exp. Med. (2000)

Bottom Line: Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature.The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36.DBL2delta was found to mediate additional binding to PECAM-1/CD31.

View Article: PubMed Central - PubMed

Affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, The Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden.

ABSTRACT
Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36. DBL2delta was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.

Show MeSH

Related in: MedlinePlus

Schematic summary of the different binding activities of the DBL1α, CIDR1α, and DBL2δ domains of PfEMP1 encoded by FCR3S1.2var1. P. falciparum expresses PfEMP1 molecules (here shown corkscrew-like) on a knob-like structure at the infected erythrocyte surface. The DBL1α domain participates in rosetting through binding to an HS-like GAG and to the blood group A antigen. The CIDR1α domain binds to CD36 and to members of the immunoglobulin superfamily, including IgM and PECAM-1/CD31, whereas the DBL2δ domain binds mainly to PECAM-1/CD31.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1887712&req=5

Figure 5: Schematic summary of the different binding activities of the DBL1α, CIDR1α, and DBL2δ domains of PfEMP1 encoded by FCR3S1.2var1. P. falciparum expresses PfEMP1 molecules (here shown corkscrew-like) on a knob-like structure at the infected erythrocyte surface. The DBL1α domain participates in rosetting through binding to an HS-like GAG and to the blood group A antigen. The CIDR1α domain binds to CD36 and to members of the immunoglobulin superfamily, including IgM and PECAM-1/CD31, whereas the DBL2δ domain binds mainly to PECAM-1/CD31.

Mentions: In conclusion, the data here show that three PfEMP1 domains (DBL1α, CIDR1α, and DBL2δ) of one PfEMP1 species mediate multiple independent interactions with a diverse set of host receptors, as summarized in Fig. 5. The findings provide a molecular explanation of the multiadhesive phenotype of P. falciparum and suggest its importance in the development of severe malaria. The DBL1α-CIDR1α head structure may also prove to be an important vaccine candidate, particularly if antibodies directed to conserved determinants in DBL1α-CIDR1α are common in those protected against severe malaria.


The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors.

Chen Q, Heddini A, Barragan A, Fernandez V, Pearce SF, Wahlgren M - J. Exp. Med. (2000)

Schematic summary of the different binding activities of the DBL1α, CIDR1α, and DBL2δ domains of PfEMP1 encoded by FCR3S1.2var1. P. falciparum expresses PfEMP1 molecules (here shown corkscrew-like) on a knob-like structure at the infected erythrocyte surface. The DBL1α domain participates in rosetting through binding to an HS-like GAG and to the blood group A antigen. The CIDR1α domain binds to CD36 and to members of the immunoglobulin superfamily, including IgM and PECAM-1/CD31, whereas the DBL2δ domain binds mainly to PECAM-1/CD31.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887712&req=5

Figure 5: Schematic summary of the different binding activities of the DBL1α, CIDR1α, and DBL2δ domains of PfEMP1 encoded by FCR3S1.2var1. P. falciparum expresses PfEMP1 molecules (here shown corkscrew-like) on a knob-like structure at the infected erythrocyte surface. The DBL1α domain participates in rosetting through binding to an HS-like GAG and to the blood group A antigen. The CIDR1α domain binds to CD36 and to members of the immunoglobulin superfamily, including IgM and PECAM-1/CD31, whereas the DBL2δ domain binds mainly to PECAM-1/CD31.
Mentions: In conclusion, the data here show that three PfEMP1 domains (DBL1α, CIDR1α, and DBL2δ) of one PfEMP1 species mediate multiple independent interactions with a diverse set of host receptors, as summarized in Fig. 5. The findings provide a molecular explanation of the multiadhesive phenotype of P. falciparum and suggest its importance in the development of severe malaria. The DBL1α-CIDR1α head structure may also prove to be an important vaccine candidate, particularly if antibodies directed to conserved determinants in DBL1α-CIDR1α are common in those protected against severe malaria.

Bottom Line: Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature.The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36.DBL2delta was found to mediate additional binding to PECAM-1/CD31.

View Article: PubMed Central - PubMed

Affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, The Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden.

ABSTRACT
Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36. DBL2delta was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.

Show MeSH
Related in: MedlinePlus