Protein Native State Stabilization by Placing Aromatic Side Chains in N-Glycosylated Reverse Turns

By Elizabeth Culyba, J. Price, S. Hanson, A. Dhar, Chi‐Huey Wong, Martin Gruebele, E. Powers, J. Kelly. 2011

163 citations recorded by the source corpus.

Protein reverse turns that interact with a phenlyalanine group allow stable introduction of glycan groups at asparagine residues. N-glycosylation of eukaryotic proteins helps them fold and traverse the cellular secretory pathway and can increase their stability, although the molecular basis for stabilization is poorly understood. Glycosylation of proteins at naïve sites (ones that normally are not glycosylated) could be useful for therapeutic and research applications but currently results in unpredictable changes to protein stability. We show that placing a phenylalanine residue two or three positions before a glycosylated asparagine in distinct reverse turns facilitates stabilizing interactions between the aromatic side chain and the first N-acetylglucosamine of the glycan. Glycosylating this portable structural module, an enhanced aromatic sequon, in three different proteins stabilizes their native states by –0.7 to –2.0 kilocalories per mole and increases cellular glycosylation efficiency.

Subfields: Molecular Biology, Organic Chemistry

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In Molecular Biology

1. A. Varki
2. M. Aebi
3. R. Schauer

In Organic Chemistry

1. A. Varki
2. M. Aebi

Citations in the corpus

• Biological roles of glycans (2016, background): “For example, experimentally placing a phenylalanine residue two or three positions before a glycosylated asparagine in distinct reverse turns facilitates stabilizing interactions between the aromatic side chain and the first GlcNAc residue of the glycan, while increasing glycosylation efficiency (49”
• Mechanisms and principles of N-linked protein glycosylation. (2011, background): “Hydrophilic N-glycans are major contributors to thermodynamic stability and solubility of proteins [51,52 ,53].”