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Antibody Multispecificity Mediated by Conformational Diversity
Abstract
A single antibody was shown to adopt different binding-site conformations and thereby bind unrelated antigens. Analysis by both x-ray crystallography and pre–steady-state kinetics revealed an equilibrium between different preexisting isomers, one of which possessed a promiscuous, low-affinity binding site for aromatic ligands, including the immunizing hapten. A subsequent induced-fit isomerization led to high-affinity complexes with a deep and narrow binding site. A protein antigen identified by repertoire selection made use of an unrelated antibody isomer with a wide, shallow binding site. Conformational diversity, whereby one sequence adopts multiple structures and multiple functions, can increase the effective size of the antibody repertoire but may also lead to autoimmunity and allergy.
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Cites
Multiple diverse ligands binding at a single protein site: A matter of pre‐existing populations
Ma, B., Shatsky, M., Wolfson, H. J., & Nussinov, R. (2002) · Protein Science · doi:10.1110/ps.21302 · Cited by 420
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Conant, G. C., & Wolfe, K. H. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2482 · Cited by 1,281
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Galli, S. J., Kalesnikoff, J., Grimbaldeston, M. A., Piliponsky, A. M., Williams, C. M. M., & Tsai, M. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141025 · Cited by 1,017
Protein Dynamism and Evolvability
Tokuriki, N., & Tawfik, D. S. (2009) · Science · doi:10.1126/science.1169375 · Cited by 940
Self-citationShowing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling
Uversky, V. N., Oldfield, C. J., & Dunker, A. K. (2005) · Journal of Molecular Recognition · doi:10.1002/jmr.747 · Cited by 847
Metadata
- Authors
- James, L. C., Roversi, P., & Tawfik, D. S.
- Venue
- Science
- Published
- 2003-02-28
- Volume
- 299
- Issue
- 5611
- Pages
- 1362-1367
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1964126053
- Cited by
- 719
- References
- 1
- FWCI
- 37.51
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.