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Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer
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Parker, Joanne L., Corey, Robin A., Stansfeld, Phillip J. and Newstead, Simon (2019) Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer. Nature Communications, 10 . 4657. doi:10.1038/S41467-019-12673-w ISSN 2041-1723.
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WRAP-structural-basis-substrate-specificity-sugar-transporters-bilayer-Stansfeld-2019.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (1879Kb) |
Official URL: https://doi.org/10.1038/S41467-019-12673-w
Abstract
Nucleotide sugars are the activated form of monosaccharides used by glycosyltransferases during glycosylation. In eukaryotes the SLC35 family of solute carriers are responsible for their selective uptake into the Endoplasmic Reticulum or Golgi apparatus. The structure of the yeast GDP-mannose transporter, Vrg4, revealed a requirement for short chain lipids and a marked difference in transport rate between the nucleotide sugar and nucleoside monophosphate, suggesting a complex network of regulatory elements control transport into these organelles. Here we report the crystal structure of the GMP bound complex of Vrg4, revealing the molecular basis for GMP recognition and transport. Molecular dynamics, combined with biochemical analysis, reveal a lipid mediated dimer interface and mechanism for coordinating structural rearrangements during transport. Together these results provide further insight into how SLC35 family transporters function within the secretory pathway and sheds light onto the role that membrane lipids play in regulating transport across the membrane.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
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Library of Congress Subject Headings (LCSH): | Nucleotides , Glycosylation, Endoplasmic reticulum, Molecular dynamics, Membrane lipids | ||||||||||||||||||||||||||||||
Journal or Publication Title: | Nature Communications | ||||||||||||||||||||||||||||||
Publisher: | Nature Publishing Group | ||||||||||||||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||||||||||||||
Official Date: | 11 October 2019 | ||||||||||||||||||||||||||||||
Dates: |
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Volume: | 10 | ||||||||||||||||||||||||||||||
Article Number: | 4657 | ||||||||||||||||||||||||||||||
DOI: | 10.1038/S41467-019-12673-w | ||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||
Date of first compliant deposit: | 1 October 2019 | ||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 14 October 2019 | ||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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