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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Research Article|
July 12 2013
Molecular determinants of co- and post-translational N-glycosylation of type I transmembrane peptides
Heidi L. H. Malaby;
Heidi L. H. Malaby
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.
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William R. Kobertz
William R. Kobertz
1
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.
1To whom correspondence should be addressed (email william.kobertz@umassmed.edu).
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Publisher: Portland Press Ltd
Received:
January 03 2013
Revision Received:
May 13 2013
Accepted:
May 29 2013
Accepted Manuscript online:
May 29 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 453 (3): 427–434.
Article history
Received:
January 03 2013
Revision Received:
May 13 2013
Accepted:
May 29 2013
Accepted Manuscript online:
May 29 2013
Citation
Heidi L. H. Malaby, William R. Kobertz; Molecular determinants of co- and post-translational N-glycosylation of type I transmembrane peptides. Biochem J 1 August 2013; 453 (3): 427–434. doi: https://doi.org/10.1042/BJ20130028
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