| Structural highlights
Function
GMT1_YEAST Involved in the import of GDP-mannose from the cytoplasm into the Golgi lumen. Defective copy causes severe glycosylation defect and abnormal retention of soluble endoplasmic reticulum proteins. Involved in vanadate sensitivity.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]
Publication Abstract from PubMed
Glycosylation is a fundamental cellular process that, in eukaryotes, occurs in the lumen of both the Golgi apparatus and the endoplasmic reticulum. Nucleotide sugar transporters (NSTs) are an essential component of the glycosylation pathway, providing the diverse range of substrates required for the glycosyltransferases. NSTs are linked to several developmental and immune disorders in humans, and in pathogenic microbes they have an important role in virulence. 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.
Structural basis of nucleotide sugar transport across the Golgi membrane.,Parker JL, Newstead S Nature. 2017 Nov 23;551(7681):521-524. doi: 10.1038/nature24464. Epub 2017 Nov, 15. PMID:29143814[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Abe M, Hashimoto H, Yoda K. Molecular characterization of Vig4/Vrg4 GDP-mannose transporter of the yeast Saccharomyces cerevisiae. FEBS Lett. 1999 Sep 24;458(3):309-12. PMID:10570930
- ↑ Gao XD, Nishikawa A, Dean N. Identification of a conserved motif in the yeast golgi GDP-mannose transporter required for binding to nucleotide sugar. J Biol Chem. 2001 Feb 9;276(6):4424-32. Epub 2000 Nov 6. PMID:11067855 doi:https://dx.doi.org/10.1074/jbc.M009114200
- ↑ Hashimoto H, Abe M, Hirata A, Noda Y, Adachi H, Yoda K. Progression of the stacked Golgi compartments in the yeast Saccharomyces cerevisiae by overproduction of GDP-mannose transporter. Yeast. 2002 Dec;19(16):1413-24. PMID:12478588 doi:https://dx.doi.org/10.1002/yea.925
- ↑ Abe M, Noda Y, Adachi H, Yoda K. Localization of GDP-mannose transporter in the Golgi requires retrieval to the endoplasmic reticulum depending on its cytoplasmic tail and coatomer. J Cell Sci. 2004 Nov 1;117(Pt 23):5687-96. Epub 2004 Oct 19. PMID:15494368 doi:https://dx.doi.org/10.1242/jcs.01491
- ↑ Ballou L, Hitzeman RA, Lewis MS, Ballou CE. Vanadate-resistant yeast mutants are defective in protein glycosylation. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3209-12. PMID:2014241
- ↑ Kanik-Ennulat C, Neff N. Vanadate-resistant mutants of Saccharomyces cerevisiae show alterations in protein phosphorylation and growth control. Mol Cell Biol. 1990 Mar;10(3):898-909. PMID:2137555
- ↑ Kanik-Ennulat C, Montalvo E, Neff N. Sodium orthovanadate-resistant mutants of Saccharomyces cerevisiae show defects in Golgi-mediated protein glycosylation, sporulation and detergent resistance. Genetics. 1995 Jul;140(3):933-43. PMID:7672592
- ↑ Dean N. Yeast glycosylation mutants are sensitive to aminoglycosides. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1287-91. PMID:7877969
- ↑ Poster JB, Dean N. The yeast VRG4 gene is required for normal Golgi functions and defines a new family of related genes. J Biol Chem. 1996 Feb 16;271(7):3837-45. PMID:8632002
- ↑ Manas P, Olivero I, Avalos M, Hernandez LM. Isolation of new nonconditional Saccharomyces cerevisiae mutants defective in asparagine-linked glycosylation. Glycobiology. 1997 Jun;7(4):487-97. PMID:9184829
- ↑ Mondesert G, Clarke DJ, Reed SI. Identification of genes controlling growth polarity in the budding yeast Saccharomyces cerevisiae: a possible role of N-glycosylation and involvement of the exocyst complex. Genetics. 1997 Oct;147(2):421-34. PMID:9335583
- ↑ Dean N, Zhang YB, Poster JB. The VRG4 gene is required for GDP-mannose transport into the lumen of the Golgi in the yeast, Saccharomyces cerevisiae. J Biol Chem. 1997 Dec 12;272(50):31908-14. PMID:9395539
- ↑ Parker JL, Newstead S. Structural basis of nucleotide sugar transport across the Golgi membrane. Nature. 2017 Nov 23;551(7681):521-524. doi: 10.1038/nature24464. Epub 2017 Nov, 15. PMID:29143814 doi:https://dx.doi.org/10.1038/nature24464
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