2z8v
From Proteopedia
(New page: 200px<br /><applet load="2z8v" size="350" color="white" frame="true" align="right" spinBox="true" caption="2z8v, resolution 2.35Å" /> '''Structure of an IgNA...) |
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==Overview== | ==Overview== | ||
| - | Apical membrane antigen 1 (AMA1) is essential for invasion of erythrocytes | + | 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. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Structure of an IgNAR-AMA1 | + | Structure of an IgNAR-AMA1 complex: targeting a conserved hydrophobic cleft broadens malarial strain recognition., Henderson KA, Streltsov VA, Coley AM, Dolezal O, Hudson PJ, Batchelor AH, Gupta A, Bai T, Murphy VJ, Anders RF, Foley M, Nuttall SD, Structure. 2007 Nov;15(11):1452-66. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17997971 17997971] |
[[Category: Orectolobus maculatus]] | [[Category: Orectolobus maculatus]] | ||
[[Category: Plasmodium falciparum 3d7]] | [[Category: Plasmodium falciparum 3d7]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Batchelor, A | + | [[Category: Batchelor, A H.]] |
| - | [[Category: Coley, A | + | [[Category: Coley, A M.]] |
| - | [[Category: Henderson, K | + | [[Category: Henderson, K A.]] |
| - | [[Category: Nuttall, S | + | [[Category: Nuttall, S D.]] |
| - | [[Category: Streltsov, V | + | [[Category: Streltsov, V A.]] |
[[Category: 14i-1]] | [[Category: 14i-1]] | ||
[[Category: ama1-vnar complex]] | [[Category: ama1-vnar complex]] | ||
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[[Category: receptor]] | [[Category: receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:00:49 2008'' |
Revision as of 17:00, 21 February 2008
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Structure of an IgNAR-AMA1 complex
Overview
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.
About this Structure
2Z8V is a Protein complex structure of sequences from Orectolobus maculatus and Plasmodium falciparum 3d7. Full crystallographic information is available from OCA.
Reference
Structure of an IgNAR-AMA1 complex: targeting a conserved hydrophobic cleft broadens malarial strain recognition., Henderson KA, Streltsov VA, Coley AM, Dolezal O, Hudson PJ, Batchelor AH, Gupta A, Bai T, Murphy VJ, Anders RF, Foley M, Nuttall SD, Structure. 2007 Nov;15(11):1452-66. PMID:17997971
Page seeded by OCA on Thu Feb 21 19:00:49 2008
