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2nyy
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(New page: 200px<br /> <applet load="2nyy" size="450" color="white" frame="true" align="right" spinBox="true" caption="2nyy, resolution 2.61Å" /> '''Crystal structure o...)
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Revision as of 07:44, 18 November 2007
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Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody CR1
Overview
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.
About this Structure
2NYY is a Single protein structure of sequence from Clostridium botulinum with ZN and CA as ligands. Full crystallographic information is available from OCA.
Reference
Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin., Garcia-Rodriguez C, Levy R, Arndt JW, Forsyth CM, Razai A, Lou J, Geren I, Stevens RC, Marks JD, Nat Biotechnol. 2007 Jan;25(1):107-16. Epub 2006 Dec 17. PMID:17173035
Page seeded by OCA on Sun Nov 18 09:51:47 2007
