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| {{STRUCTURE_2nyy| PDB=2nyy | SCENE= }} | | {{STRUCTURE_2nyy| PDB=2nyy | SCENE= }} |
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| '''Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody CR1'''
| | ===Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody CR1=== |
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| ==Overview==
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| Broadening antibody specificity without compromising affinity should facilitate detection and neutralization of toxin and viral subtypes. We used yeast display and a co-selection strategy to increase cross-reactivity of a single chain (sc) Fv antibody to botulinum neurotoxin type A (BoNT/A). Starting with a scFv that binds the BoNT/A1 subtype with high affinity (136 pM) and the BoNT/A2 subtype with low affinity (109 nM), we increased its affinity for BoNT/A2 1,250-fold, to 87 pM, while maintaining high-affinity binding to BoNT/A1 (115 pM). To find the molecular basis for improved cross-reactivity, we determined the X-ray co-crystal structures of wild-type and cross-reactive antibodies complexed to BoNT/A1 at resolutions up to 2.6 A, and measured the thermodynamic contribution of BoNT/A1 and A2 amino acids to wild-type and cross-reactive antibody binding. The results show how an antibody can be engineered to bind two different antigens despite structural differences in the antigen-antibody interface and may provide a general strategy for tuning antibody specificity and cross-reactivity.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17173035}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17173035 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17173035}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Neurotoxin]] | | [[Category: Neurotoxin]] |
| [[Category: Protein antibody complex]] | | [[Category: Protein antibody complex]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:05:48 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:58:26 2008'' |
