Journal article
Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-019-12673-w
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Communications More from this journal
- Volume:
- 10
- Article number:
- 4657
- Publication date:
- 2019-10-11
- Acceptance date:
- 2019-09-24
- DOI:
- EISSN:
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2041-1723
- Pmid:
-
31604945
- Language:
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English
- Keywords:
- Pubs id:
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pubs:1063277
- UUID:
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uuid:9fa820c8-9dc9-44ee-9fd4-91045d23713e
- Local pid:
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pubs:1063277
- Source identifiers:
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1063277
- Deposit date:
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2019-11-14
Terms of use
- Copyright holder:
- Parker et al
- Copyright date:
- 2019
- Notes:
- Copyright © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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