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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...

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Autores principales: Parker, Joanne L, Newstead, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
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.
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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
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