2Y8D: Structure Of Dbl6 Epsilon Domain From Var2csa Strain Fcr3

Citation:
Abstract
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a family of adhesins of the falciparum species of the malaria parasite, is exposed on the surface of the infected erythrocyte. In general, only one PfEMP1 variant is expressed at a time but switching between variants occurs, changing both host-cell receptor specificity and serotype. The PfEMP1 variant VAR2CSA causes sequestration of infected erythrocytes in the intervillous spaces of the placenta via the glycosaminoglycan chondroitin sulfate A. This leads to pregnancy-associated malaria, which has severe consequences for the fetus and mother. The extracellular region of VAR2CSA comprises six DBL (Duffy-binding-like) domains and a single CIDR (cysteine-rich inter-domain region) domain. The C-terminal domain DBL6epsilon, the most polymorphic domain of VAR2CSA, has seven regions of high variability termed variable blocks (VBs). Here we have determined the crystal structure of DBL6epsilon from the FCR3 parasite line and have compared it with the previously determined structure of that from the 3D7 line. We found significant differences particularly in the N-terminal region, which contains the first VB (VB1). Although DBL6epsilon is the most variable VAR2CSA domain, DBL6epsilon-FCR3 and DBL6epsilon-3D7 react with IgG purified from immune sera of pregnant women. Furthermore, IgG purified on one domain cross-reacts with the other, confirming the presence of cross-reactive epitopes. We also examined reactivity of immune sera to the four least variable VB (VB1, VB2, VB4 and VB5) using peptides with the consensus sequence closest, in turn, to the FCR3 or 3D7 domain. These results provide new molecular insights into immune escape by parasites expressing the VAR2CSA variant.
PDB ID: 2Y8DDownload
MMDB ID: 97202
PDB Deposition Date: 2011/2/4
Updated in MMDB: 2013/05
Experimental Method:
x-ray diffraction
Resolution: 1.84  Å
Source Organism:
Similar Structures:
Biological Unit for 2Y8D: monomeric; determined by author and by software (PISA)
Molecular Components in 2Y8D
Label Count Molecule
Protein (1 molecule)
1
Erythrocyte Membrane Protein 1
Molecule annotation
Chemicals (3 molecules)
1
2
2
1
* Click molecule labels to explore molecular sequence information.

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