Department of Biochemistry, Biophysics and Molecular Biology - Iowa State University

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Host:  Adam Barb

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"Elucidating How N-glycosylation Impacts Immunoglobulin G Fc Structure and Receptor Binding"

N-linked glycans are post-translational modifications that link an oligosaccharide to an asparagine residue. The attached oligosaccharide then undergoes extensive modification in the Golgi apparatus prior to protein secretion.  This type of modification helps with protein folding, resistance to protease activity, immunogenicity, and imparting biological activity.  Antibodies, such as IgG1, offer an idealized system to study proteins containing an N-linked glycan.

In this work we seek to understand how this cellular response is modulated by the N-linked glycans present on the Fc region.  The Fc contains two N-linked glycans, which are attached in a region that is critical for immune receptor binding.  It is thought that these glycans, through contacts across a beta sheet, restrict the motion of a loop region allowing for a high affinity interaction between the Fc region and immune receptors.  Through NMR and X–ray crystallography studies we show that one specific loop becomes mobile when the glycan is truncated and that when a full glycan is present the loops moves by more than 5Å.  Fc with the truncated N-glycan binds receptor with 100-fold less affinity that Fc with a full glycan and thus this reorganization is incredibly important to understanding complex formation.

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