2z8v

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

Revision as of 04:43, 28 July 2008

Image:2z8v.png

Template:STRUCTURE 2z8v

Structure of an IgNAR-AMA1 complex

Template:ABSTRACT PUBMED 17997971

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

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