Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin.

Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Research Abstract Details 

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Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Abstract Text:

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.

Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Publishing Authors By Initials

For similar protein interaction mapping research abstracts see: protein interaction mapping research

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Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Nature biotechnology

VOLUME: 25

Page Numbers: 107-16

Journal Abbreviation: Nat. Biotechnol.

ISSN: 1087-0156

DAY: 17

MONTH: 12

YEAR: 2006

Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9604648

Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Keywords Mesh Terms:

KEYWORDS: Protein Interaction Mapping

MESH TERMS: methods

Chemical & Substance for Abstract: Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Information

Substance Name: Botulinum Toxin Type A

Registry Number: 0

Grant and Affiliation Information for Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin.

AFFILIATION: Department of Anesthesia and Pharmaceutical Chemistry, University of California, San Francisco Rm. 3C-38, San Francisco General Hospital, 1001 Potrero Ave., San Francisco, California 94110, USA.

Country: United States

AGENCY: United States NIAID

GRANT: U54 AI065359

ACRONYM: AI

MEDLINETA: Nat Biotechnol

REFSOURCE: Nat Biotechnol. 2007 Jan;25(1):63-5

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