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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2007-11-13
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pubmed:databankReference |
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pubmed:abstractText |
Apical membrane antigen 1 (AMA1) is essential for invasion of erythrocytes and hepatocytes by Plasmodium parasites and is a leading malarial vaccine candidate. Although conventional antibodies to AMA1 can prevent such invasion, extensive polymorphisms within surface-exposed loops may limit the ability of these AMA1-induced antibodies to protect against all parasite genotypes. Using an AMA1-specific IgNAR single-variable-domain antibody, we performed targeted mutagenesis and selection against AMA1 from three P. falciparum strains. We present cocrystal structures of two antibody-AMA1 complexes which reveal extended IgNAR CDR3 loops penetrating deep into a hydrophobic cleft on the antigen surface and contacting residues conserved across parasite species. Comparison of a series of affinity-enhancing mutations allowed dissection of their relative contributions to binding kinetics and correlation with inhibition of erythrocyte invasion. These findings provide insights into mechanisms of single-domain antibody binding, and may enable design of reagents targeting otherwise cryptic epitopes in pathogen antigens.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0969-2126
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pubmed:author |
pubmed-author:AndersRobin FRF,
pubmed-author:BaiTaoT,
pubmed-author:BatchelorAdrian HAH,
pubmed-author:ColeyAndrew MAM,
pubmed-author:DolezalOlanO,
pubmed-author:FoleyMichaelM,
pubmed-author:GuptaAditiA,
pubmed-author:HendersonKylie AKA,
pubmed-author:HudsonPeter JPJ,
pubmed-author:MurphyVincent JVJ,
pubmed-author:NuttallStewart DSD,
pubmed-author:StreltsovVictor AVA
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pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1452-66
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17997971-Amino Acid Sequence,
pubmed-meshheading:17997971-Animals,
pubmed-meshheading:17997971-Antibodies, Protozoan,
pubmed-meshheading:17997971-Antibody Affinity,
pubmed-meshheading:17997971-Antigens, Protozoan,
pubmed-meshheading:17997971-Base Sequence,
pubmed-meshheading:17997971-Binding Sites,
pubmed-meshheading:17997971-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:17997971-Immunoglobulin Variable Region,
pubmed-meshheading:17997971-Kinetics,
pubmed-meshheading:17997971-Malaria, Falciparum,
pubmed-meshheading:17997971-Membrane Proteins,
pubmed-meshheading:17997971-Models, Molecular,
pubmed-meshheading:17997971-Molecular Sequence Data,
pubmed-meshheading:17997971-Peptide Library,
pubmed-meshheading:17997971-Plasmodium falciparum,
pubmed-meshheading:17997971-Protein Structure, Tertiary,
pubmed-meshheading:17997971-Protozoan Proteins,
pubmed-meshheading:17997971-Surface Plasmon Resonance
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pubmed:year |
2007
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pubmed:articleTitle |
Structure of an IgNAR-AMA1 complex: targeting a conserved hydrophobic cleft broadens malarial strain recognition.
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pubmed:affiliation |
CSIRO Molecular and Health Technologies, 343 Royal Parade, Parkville 3052, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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