The 1/3 of the human proteome that traverses the secretory pathway is generally co-translationally N-glycosylated at Asn within the Asn-Xxx-Thr/Ser sequon in the lumen of the endoplasmic reticulum. We have shown that placing an aromatic residue two-three positions prior to a N-glycosylated Asn in specific reverse turn types enables significant stabilizing hydrophobic interactions between the aromatic side chain, the first N-acetylglucosamine (GlcNAc) of the glycan and the Thr side chain.  Glycosylation of a specific �enhanced aromatic sequon� in the complementary reverse turn type substantially stabilizes the native state of several different glycosylation-na�ve proteins. This approach for native state stabilization will be compared to and contrasted with the incorporation of Beta-turn mimics into four-residue reverse turns in place of the i+1 and i+2 residues. Beta-turn incorporation is envisioned to nucleate folding by pre-organizing the flanking polypeptide chains through hydrophobic interactions and/or conformational constraints, thereby lowering the activation barrier for beta-sheet formation.

Strategic incorporation of N-glycans and backbone replacements into reverse turns to enhance protein energetics

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.