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Structural characterization of a human Fc fragment engineered for lack of effector functions

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Oganesyan, Vaheh, Gao, Changshou, Shirinian, Lena, Wu, Herren, Dall'Acqua, William F.·2008·Acta Crystallographica Section D Biological Crystallography

Abstract

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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CoChat. (2026). Citation check: Structural characterization of a human Fc fragment engineered for lack of effector functions. https://app.cochat.ai/papers/10.1107/s0907444908007877
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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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