Ribophorin I regulates substrate delivery to the oligosaccharyltransferase core
Open Access
- 15 July 2008
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (28), 9534-9539
- https://doi.org/10.1073/pnas.0711846105
Abstract
Protein N-glycosylation is widespread among biological systems, and the fundamental process of transferring a lipid-linked glycan to suitable asparagine residues of newly synthesized proteins occurs in both prokaryotes and eukaryotes. The core reaction is mediated by Stt3p family members, and in many organisms this component alone is sufficient to constitute the so called oligosaccharyltransferase (OST). However, eukaryotes typically have a more elaborate OST with several additional subunits of poorly defined function. In the mammalian OST complex one such subunit, ribophorin I, is proposed to facilitate the N-glycosylation of certain precursors during their biogenesis at the endoplasmic reticulum. Here, we use cell culture models to show that ribophorin I depletion results in substrate-specific defects in N-glycosylation, clearly establishing a defined physiological role for ribophorin I. To address the molecular mechanism of ribophorin I function, a cross-linking approach was used to explore the environment of nascent glycoproteins during the N-glycosylation reaction. We show for the first time that ribophorin I can regulate the delivery of precursor proteins to the OST complex by capturing substrates and presenting them to the catalytic core.Keywords
This publication has 34 references indexed in Scilit:
- Structure of the Oligosaccharyl Transferase Complex at 12 Å ResolutionStructure, 2008
- Structure-guided identification of a new catalytic motif of oligosaccharyltransferaseThe EMBO Journal, 2007
- Dolichol-linked oligosaccharide selection by the oligosaccharyltransferase in protist and fungal organismsThe Journal of cell biology, 2007
- Ribophorin I acts as a substrate-specific facilitator of N-glycosylationJournal of Cell Science, 2007
- Dimeric organization of the yeast oligosaccharyl transferase complexProceedings of the National Academy of Sciences of the United States of America, 2006
- Definition of the bacterial N-glycosylation site consensus sequenceThe EMBO Journal, 2006
- Ribophorin I Associates with a Subset of Membrane Proteins after Their Integration at the Sec61 TransloconPublished by Elsevier BV ,2005
- Systematic functional analysis of the Caenorhabditis elegans genome using RNAiNature, 2003
- Pivotal Role of Calnexin and Mannose Trimming in Regulating the Endoplasmic Reticulum-associated Degradation of Major Histocompatibility Complex Class I Heavy ChainPublished by Elsevier BV ,2000
- Characterization of the ribosomal binding site in rat liver rough microsomes: Ribophorins I and II, two integral membrane proteins related to ribosome bindingJournal of Supramolecular Structure, 1978