title: Molecular determinants of co- and post-translational N-glycosylation of type I transmembrane peptides.
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.
authors.affiliation: Department 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.
authors.forename: Heidi L H
authors.initials: HL
authors.lastname: Malaby
authors.forename: William R
authors.initials: WR
authors.lastname: Kobertz
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006031:Glycosylation; D006602:Hexosyltransferases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: C489622:KCNE1 protein, human; C489619:KCNE2 protein, human; C418492:KCNE3 protein, human; C498897:KCNE4 protein, human; C502068:KCNE5 protein, human; D008565:Membrane Proteins; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D006602:Hexosyltransferases; C025620:dolichyl-diphosphooligosaccharide - protein glycotransferase