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Structural basis of nucleotide sugar transport across the Golgi membrane
Glycosylation is a fundamental cellular process that in eukaryotes occurs in the lumen of both the Golgi apparatus and endoplasmic reticulum 1. Nucleotide sugar transporters (NSTs) are an essential component of the glyscosylation pathway, providing the diverse range of substrates required for the gl...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701743/ https://www.ncbi.nlm.nih.gov/pubmed/29143814 http://dx.doi.org/10.1038/nature24464 |
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author | Parker, Joanne L Newstead, Simon |
author_facet | Parker, Joanne L Newstead, Simon |
author_sort | Parker, Joanne L |
collection | PubMed |
description | Glycosylation is a fundamental cellular process that in eukaryotes occurs in the lumen of both the Golgi apparatus and endoplasmic reticulum 1. Nucleotide sugar transporters (NSTs) are an essential component of the glyscosylation pathway, providing the diverse range of substrates required for the glycosyltransferases 2,3. NSTs are linked to several developmental and immune disorders in humans and in pathogenic microbes play an important role in virulence 4–8. How NSTs recognise and transport activated monosaccharides however is currently unclear. Here we present the first crystal structure of an NST, the GDP-mannose transporter Vrg4, in both the substrate free and bound states. A hitherto unobserved requirement for short chain lipids in activating the transporter supports a model for regulation within the highly dynamic membranes of the Golgi apparatus. Our results provide a structural basis for understanding nucleotide sugar recognition and provide insights into the transport and regulatory mechanism for this family of intracellular transporters. |
format | Online Article Text |
id | pubmed-5701743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-57017432018-05-15 Structural basis of nucleotide sugar transport across the Golgi membrane Parker, Joanne L Newstead, Simon Nature Article Glycosylation is a fundamental cellular process that in eukaryotes occurs in the lumen of both the Golgi apparatus and endoplasmic reticulum 1. Nucleotide sugar transporters (NSTs) are an essential component of the glyscosylation pathway, providing the diverse range of substrates required for the glycosyltransferases 2,3. NSTs are linked to several developmental and immune disorders in humans and in pathogenic microbes play an important role in virulence 4–8. How NSTs recognise and transport activated monosaccharides however is currently unclear. Here we present the first crystal structure of an NST, the GDP-mannose transporter Vrg4, in both the substrate free and bound states. A hitherto unobserved requirement for short chain lipids in activating the transporter supports a model for regulation within the highly dynamic membranes of the Golgi apparatus. Our results provide a structural basis for understanding nucleotide sugar recognition and provide insights into the transport and regulatory mechanism for this family of intracellular transporters. 2017-11-15 2017-11-23 /pmc/articles/PMC5701743/ /pubmed/29143814 http://dx.doi.org/10.1038/nature24464 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Parker, Joanne L Newstead, Simon Structural basis of nucleotide sugar transport across the Golgi membrane |
title | Structural basis of nucleotide sugar transport across the Golgi
membrane |
title_full | Structural basis of nucleotide sugar transport across the Golgi
membrane |
title_fullStr | Structural basis of nucleotide sugar transport across the Golgi
membrane |
title_full_unstemmed | Structural basis of nucleotide sugar transport across the Golgi
membrane |
title_short | Structural basis of nucleotide sugar transport across the Golgi
membrane |
title_sort | structural basis of nucleotide sugar transport across the golgi
membrane |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701743/ https://www.ncbi.nlm.nih.gov/pubmed/29143814 http://dx.doi.org/10.1038/nature24464 |
work_keys_str_mv | AT parkerjoannel structuralbasisofnucleotidesugartransportacrossthegolgimembrane AT newsteadsimon structuralbasisofnucleotidesugartransportacrossthegolgimembrane |