Structural highlights
Publication Abstract from PubMedThe Fc region of IgG antibodies (Cgamma2 and Cgamma3 domains) is responsible for effector functions such as antibody-dependent cell-mediated cytotoxicity and phagocytosis, through engagement with Fcgamma receptors, although the ability to elicit these functions differs between the four human IgG subclasses. A key determinant of Fcgamma receptor interactions is the FG loop in the Cgamma2 domain. High resolution cryogenic IgG4-Fc crystal structures have revealed a unique conformation for this loop, which could contribute to the particular biological properties of this subclass. To further explore the conformation of the IgG4 Cgamma2 FG loop at near-physiological temperature, we solved a 2.7A resolution room temperature structure of recombinant human IgG4-Fc from crystals analysed in situ. The Cgamma2 FG loop in one chain differs from the cryogenic structure, and adopts the conserved conformation found in IgG1-Fc; however, this conformation participates in extensive crystal packing interactions. On the other hand, at room temperature, and free from any crystal packing interactions, the Cgamma2 FG loop in the other chain adopts the conformation previously observed in the cryogenic IgG4-Fc structures, despite both conformations being accessible. The room temperature human IgG4-Fc structure thus provides a more complete and physiologically relevant description of the conformation of this functionally critical Cgamma2 FG loop. Room temperature structure of human IgG4-Fc from crystals analysed in situ.,Davies AM, Rispens T, Ooijevaar-de Heer P, Aalberse RC, Sutton BJ Mol Immunol. 2017 Jan;81:85-91. doi: 10.1016/j.molimm.2016.11.021. Epub 2016 Dec , 1. PMID:27915153[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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