Protein native-state stabilization by placing aromatic side chains in N-glycosylated reverse turns

Elizabeth K. Culyba, Joshua L. Price, Sarah R. Hanson, Apratim Dhar, Chi Huey Wong, Martin Gruebele, Evan T. Powers, Jeffery W. Kelly

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)571-575
Number of pages5
JournalScience
Volume331
Issue number6017
DOIs
StatePublished - Feb 4 2011

ASJC Scopus subject areas

  • General

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