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Structural characterization of a human Fc fragment engineered for lack of effector functions
Open accessAbstract
The first three-dimensional structure of a human Fc fragment genetically engineered for the elimination of its ability to mediate antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity is reported. When introduced into the lower hinge and CH2 domain of human IgG1 molecules, the triple mutation L234F/L235E/P331S ('TM') causes a profound decrease in their binding to human CD64, CD32A, CD16 and C1q. Enzymatically produced Fc/TM fragment was crystallized and its structure was solved at a resolution of 2.3 A using molecular replacement. This study revealed that the three-dimensional structure of Fc/TM is very similar to those of other human Fc fragments in the experimentally visible region spanning residues 236-445. Thus, the dramatic broad-ranging effects of TM on IgG binding to several effector molecules cannot be explained in terms of major structural rearrangements in this portion of the Fc.
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Metadata
- Authors
- Oganesyan, V., Gao, C., Shirinian, L., Wu, H., & Dall'Acqua, W. F.
- Venue
- Acta Crystallographica Section D Biological Crystallography
- Published
- 2008-05-14
- Volume
- 64
- Issue
- 6
- Pages
- 700-704
- ISSN
- 0907-4449 (ISSN-L)
- OpenAlex
- W2039870425
- Cited by
- 197
- References
- 0
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Oganesyan, V., Gao, C., Shirinian, L., Wu, H., & Dall'Acqua, W. F. (2008). Structural characterization of a human Fc fragment engineered for lack of effector functions. Acta Crystallographica Section D Biological Crystallography. https://doi.org/10.1107/s0907444908007877
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.