| 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
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.
Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer.,Parker JL, Corey RA, Stansfeld PJ, Newstead S Nat Commun. 2019 Oct 11;10(1):4657. doi: 10.1038/s41467-019-12673-w. PMID:31604945[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:http://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:http://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:http://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, Corey RA, Stansfeld PJ, Newstead S. Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer. Nat Commun. 2019 Oct 11;10(1):4657. doi: 10.1038/s41467-019-12673-w. PMID:31604945 doi:http://dx.doi.org/10.1038/s41467-019-12673-w
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