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Updated: May 11, 2026

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
Molecular determinants of co- and post-translational N-glycosylation of type I transmembrane peptides
Heidi L H Malaby1, William R Kobertz
1Department of Biochemistry and Molecular Pharmacology, Programs in Neuroscience and Chemical Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605-2324, U.S.A.
Abstract:
Type I transmembrane peptides acquire N-linked glycans during and after protein synthesis to facilitate anterograde trafficking through the secretory pathway. Mutations in N-glycosylation consensus sites (NXT and NXS, where X≠P) that alter the kinetics of the initial N-glycan attachment have been associated with cardiac arrhythmias; however, the molecular determinants that define co- and post-translational consensus sites in proteins are not known. In the present study, we identified co- and post-translational consensus sites in the KCNE family of K+ channel regulatory subunits to uncover three determinants that favour co-translational N-glycosylation kinetics of type I transmembrane peptides which lack a cleavable signal sequence: threonine-containing consensus sites (NXT), multiple N-terminal consensus sites and long C-termini. The identification of these three molecular determinants now makes it possible to predict co- and post-translational consensus sites in type I transmembrane peptides.
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