Letter | Published:

Structural basis of nucleotide sugar transport across the Golgi membrane

Nature volume 551, pages 521524 (23 November 2017) | Download Citation

Abstract

Glycosylation is a fundamental cellular process that, in eukaryotes, occurs in the lumen of both the Golgi apparatus and the endoplasmic reticulum1. Nucleotide sugar transporters (NSTs) are an essential component of the glycosylation pathway, providing the diverse range of substrates required for the glycosyltransferases2,3. NSTs are linked to several developmental and immune disorders in humans, and in pathogenic microbes they have an important role in virulence4,5,6,7,8. How NSTs recognize and transport activated monosaccharides, however, is currently unclear. Here we present the crystal structure of an NST, the GDP–mannose transporter Vrg4, in both the substrate-free and the bound states. A hitherto unobserved requirement of 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 of this family of intracellular transporters.

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Acknowledgements

We thank the staff of beamlines I24 Diamond Light Source, UK, Proxima-2a, Soleil, France and BL1-A, Photon Factory, Japan for assistance. We thank O. Nureki and R. Ishitani for assistance in accessing BL1-A and G. Kuteyi for technical support. This work was supported by Wellcome awards (102890/Z/13/Z and 102890/Z/13/A).

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  1. 1Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK

    • Joanne L. Parker
    •  & Simon Newstead

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Contributions

J.L.P. and S.N. designed and carried out the experiments, interpreted the data and wrote the paper.

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The authors declare no competing financial interests.

Corresponding authors

Correspondence to Joanne L. Parker or Simon Newstead.

Reviewer Information Nature thanks M. Wild, J. Zimmer and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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https://doi.org/10.1038/nature24464

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