Crystal structure of sialylated IgG Fc: implications for the mechanism of intravenous immunoglobulin therapy.

Journal article

Intravenous Ig consists of pooled human serum IgG and is widely used as an antiinflammatory agent. The fraction of IgG that is α2,6-sialylated exhibits anti-inflammatory activity and sialylation is proposed to enable binding to the cell surface lectin, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) (1). In a recent article in PNAS, Sondermann et al. propose a mechanism to explain the putative sialic acid-dependent binding of IgG Fc to DC-SIGN, as well as to the IgE receptor,CD23(2).Thecoreoftheirhypothesis is that sialylation of IgG Fc leads to a conformational change, which triggers DC-SIGN binding. To directly assess this hypothesis, we have generated α2,6-sialylated IgG1 Fc (sFc) that we both chemically verified by HPLC analysis (Fig. 1A)andstructurally characterized by X-ray crystallographic analysis to a resolution of 2.3 Å (Fig. 1 B and C, and Table 1).

Authors: Crispin, M; Yu, X; Bowden, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: National Academy of Sciences
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 110
• Issue: 38
• Pages: E3544-E3546
• Publication date: 2013-09-01
• Acceptance date: 2013-08-08
• DOI: 10.1073/pnas.1310657110
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Animals; Receptors, IgG; Immunoglobulin Fc Fragments; Cell Adhesion Molecules; Lectins, C-Type; Humans; Receptors, IgE; Receptors, Cell Surface