Abstract
Immunoglobulin G (IgG) is a major serum glycoprotein that exerts the role of antibody in the immune system. This multifunctional glycoprotein couples antigen recognition with a variety of effector functions promoted via interactions with various IgG-binding proteins. Given its versatile functionality, IgG has recently been used for therapeutic interventions. Evidence indicates that the carbohydrate moieties of IgG glycoproteins critically affect their antibody functions, particularly the effector functions mediated by the interactions with Fcγ receptors (FcγRs). N-glycans at specific positions of FcγR also contribute both positively and negatively to the interactions with IgG. The integration of multilateral biophysical approaches, including X-ray crystallography, nuclear magnetic resonance spectroscopy, and molecular dynamics simulations, has provided structural insights into the mechanisms underlying the glycofunctions of this interacting system. The N-glycans of IgG and FcγR mediate their interactions by either strengthening or weakening the affinity on the basis of their glycoforms. Moreover, the N-glycosylation of IgG-Fc is a prerequisite to maintain the integrity of the quaternary structure of the sites interacting with the effector molecules and can also control functionally relevant local conformations. The biopharmaceutical significance of these glycan functions is discussed from a structural point of view.
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Acknowledgments
We would like to thank Ms. Kiyomi Senda and Ms. Kumiko Hattori (Nagoya City University) for their help with the protein purification. This work was partly supported by the Nanotechnology Platform Program (Molecule and Material Synthesis) of MEXT and MEXT/JSPS Grants in Aid for Scientific Research (JP25102008, JP15K07935, JP17H06414, JP17H05893, and JP18K14892).
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Yagi, H., Yanaka, S., Kato, K. (2018). Structure and Dynamics of Immunoglobulin G Glycoproteins. In: Yamaguchi, Y., Kato, K. (eds) Glycobiophysics. Advances in Experimental Medicine and Biology, vol 1104. Springer, Singapore. https://doi.org/10.1007/978-981-13-2158-0_11
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