Abstract
The VAR2CSA protein has been closely associated with pregnancy-associated malaria and is recognized as the main adhesin exposed on the surface of Plasmodium falciparum-infected erythrocytes. Chondroitin sulfate A was identified as the main host receptor in the placenta. Single-domain heavy-chain camelid antibodies, more commonly called nanobodies, were selected and produced against the DBL6ℇ-FCR3 domain of VAR2CSA. Crystals of two specific nanobodies, Nb2907 and Nb2919, identified as strong binders to DBL6ℇ-FCR3 and the full-length VAR2CSA exposed on the surface of FCR3 P. falciparum-infected erythrocytes, were obtained. Crystals of Nb2907 diffract to 2.45 Å resolution and belong to space group C2 with unit-cell parameters a=136.1, b=78.5, c=103.4 Å, β=118.8°, whereas Nb2919 crystals diffract to 2.15 Å resolution and belong to space group P4₃2₁2 with unit-cell parameters a=b=62.7, c=167.2 Å.
Keywords:
DBL domain; VAR2CSA; nanobody; pregnancy-associated malaria.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Protozoan / chemistry*
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Antibodies, Protozoan / genetics
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Antibodies, Protozoan / isolation & purification
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Antigens, Protozoan / chemistry*
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Antigens, Protozoan / immunology
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Binding Sites
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Camelids, New World / immunology
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Crystallography, X-Ray
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Erythrocytes / parasitology
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Escherichia coli / chemistry
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Escherichia coli / genetics
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Models, Molecular
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Molecular Sequence Data
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Plasmodium falciparum / chemistry*
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Plasmodium falciparum / metabolism
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Sequence Alignment
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Sequence Homology, Amino Acid
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Single-Domain Antibodies / chemistry*
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Single-Domain Antibodies / genetics
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Single-Domain Antibodies / isolation & purification
Substances
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Antibodies, Protozoan
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Antigens, Protozoan
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Recombinant Proteins
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Single-Domain Antibodies
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VAR2CSA protein, Plasmodium falciparum