Biological Projects

Small molecule binding to the neonatal Fc Receptor

The neonatal Fc receptor plays a crucial role in regulation of Immunoglobulin G and serum albumin catabolism and is a clinically validated drug target for the treatment of autoimmune diseases caused by pathogenic antibodies via the inhibition of its interaction with IgG. As part of a multidisciplinary research, we used fast-MAS (100 kHz) to study the binding of small molecules to heterodimers of the neonatal Fc receptor. We were able to detect ligand-induced chemical-shift perturbations for residues in the binding pocket and allosteric changes close to the interface of the two receptors in the asymmetric unit as well as potentially in the albumin interaction site. Our investigation establishes a method to characterize structurally small molecule binding to non-deuterated large proteins by NMR, even in their glycosylated form, which may prove highly valuable in structure-based drug discovery campaigns.



Stoepler D, Macpherson A, Smith-Penzel S, Basse N, Lecomte F, Deboves H, Taylor RD, Norman T, Porter J, Waters LC, Westwood M, Cossins B, Cain K, White J, Griffin R, Prosser C, Kelm S, Sullivan AH, Fox D 3rd, Carr MD, Henry A, Taylor R, Meier BH, Oschkinat H, Lawson AD (2018) Insight into small molecule binding to the neonatal Fc receptor by X-ray crystallography and 100 kHz magic-angle-spinning NMR. PLoS Biol 16(5), e2006192. DOI: 10.1371/journal.pbio.2006192

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
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