Abstract |
Dolichol is an obligate carrier of glycans for N-linked protein glycosylation, O-mannosylation, and GPI anchor biosynthesis. cis-prenyltransferase (cis-PTase) is the first enzyme committed to the synthesis of dolichol. However, the proteins responsible for mammalian cis-PTase activity have not been delineated. Here we show that Nogo-B receptor (NgBR) is a subunit required for dolichol synthesis in yeast, mice, and man. Moreover, we describe a family with a congenital disorder of glycosylation caused by a loss of function mutation in the conserved C terminus of NgBR-R290H and show that fibroblasts isolated from patients exhibit reduced dolichol profiles and enhanced accumulation of free cholesterol identically to fibroblasts from mice lacking NgBR. Mutation of NgBR-R290H in man and orthologs in yeast proves the importance of this evolutionarily conserved residue for mammalian cis-PTase activity and function. Thus, these data provide a genetic basis for the essential role of NgBR in dolichol synthesis and protein glycosylation.
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Authors | Eon Joo Park, Kariona A Grabińska, Ziqiang Guan, Viktor Stránecký, Hana Hartmannová, Kateřina Hodaňová, Veronika Barešová, Jana Sovová, Levente Jozsef, Nina Ondrušková, Hana Hansíková, Tomáš Honzík, Jiří Zeman, Helena Hůlková, Rong Wen, Stanislav Kmoch, William C Sessa |
Journal | Cell metabolism
(Cell Metab)
Vol. 20
Issue 3
Pg. 448-57
(Sep 02 2014)
ISSN: 1932-7420 [Electronic] United States |
PMID | 25066056
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Dolichols
- NUS1 protein, human
- Nogo-B receptor, mouse
- Receptors, Cell Surface
- Saccharomyces cerevisiae Proteins
- Transferases
- cis-prenyl transferase
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Topics |
- Amino Acid Sequence
- Animals
- Cells, Cultured
- Dolichols
(metabolism)
- Evolution, Molecular
- Female
- Gene Knockout Techniques
- Glycosylation
- Humans
- Male
- Metabolic Diseases
(genetics, metabolism)
- Mice
- Molecular Sequence Data
- Point Mutation
- Receptors, Cell Surface
(chemistry, genetics, metabolism)
- Saccharomyces cerevisiae
(chemistry, genetics, metabolism)
- Saccharomyces cerevisiae Proteins
(chemistry, genetics, metabolism)
- Transferases
(chemistry, genetics, metabolism)
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