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| [[Image:2z8v.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2z8v| PDB=2z8v | SCENE= }} | | {{STRUCTURE_2z8v| PDB=2z8v | SCENE= }} |
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| '''Structure of an IgNAR-AMA1 complex'''
| | ===Structure of an IgNAR-AMA1 complex=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17997971}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17997971 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17997971}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Immune system]] | | [[Category: Immune system]] |
| [[Category: Receptor]] | | [[Category: Receptor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 20:03:03 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:42:57 2008'' |
