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Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis.

Publication ,  Journal Article
Ardiccioni, C; Clarke, OB; Tomasek, D; Issa, HA; von Alpen, DC; Pond, HL; Banerjee, S; Rajashankar, KR; Liu, Q; Guan, Z; Li, C; Kloss, B ...
Published in: Nat Commun
January 5, 2016

The attachment of a sugar to a hydrophobic polyisoprenyl carrier is the first step for all extracellular glycosylation processes. The enzymes that perform these reactions, polyisoprenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which generates the mannose donor for glycosylation in the endoplasmic reticulum. Here we report the 3.0 Å resolution crystal structure of GtrB, a glucose-specific PI-GT from Synechocystis, showing a tetramer in which each protomer contributes two helices to a membrane-spanning bundle. The active site is 15 Å from the membrane, raising the question of how water-soluble and membrane-embedded substrates are brought into apposition for catalysis. A conserved juxtamembrane domain harbours disease mutations, which compromised activity in GtrB in vitro and in human DPM1 tested in zebrafish. We hypothesize a role of this domain in shielding the polyisoprenyl-phosphate for transport to the active site. Our results reveal the basis of PI-GT function, and provide a potential molecular explanation for DPM1-related disease.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 5, 2016

Volume

7

Start / End Page

10175

Location

England

Related Subject Headings

  • Zebrafish
  • Synechocystis
  • Protein Conformation
  • Models, Molecular
  • Mannosyltransferases
  • Humans
  • Glycosyltransferases
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Bacterial
  • Animals, Genetically Modified
 

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Ardiccioni, C., Clarke, O. B., Tomasek, D., Issa, H. A., von Alpen, D. C., Pond, H. L., … Mancia, F. (2016). Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat Commun, 7, 10175. https://doi.org/10.1038/ncomms10175
Ardiccioni, Chiara, Oliver B. Clarke, David Tomasek, Habon A. Issa, Desiree C. von Alpen, Heather L. Pond, Surajit Banerjee, et al. “Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis.Nat Commun 7 (January 5, 2016): 10175. https://doi.org/10.1038/ncomms10175.
Ardiccioni C, Clarke OB, Tomasek D, Issa HA, von Alpen DC, Pond HL, et al. Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat Commun. 2016 Jan 5;7:10175.
Ardiccioni, Chiara, et al. “Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis.Nat Commun, vol. 7, Jan. 2016, p. 10175. Pubmed, doi:10.1038/ncomms10175.
Ardiccioni C, Clarke OB, Tomasek D, Issa HA, von Alpen DC, Pond HL, Banerjee S, Rajashankar KR, Liu Q, Guan Z, Li C, Kloss B, Bruni R, Kloppmann E, Rost B, Manzini MC, Shapiro L, Mancia F. Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat Commun. 2016 Jan 5;7:10175.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 5, 2016

Volume

7

Start / End Page

10175

Location

England

Related Subject Headings

  • Zebrafish
  • Synechocystis
  • Protein Conformation
  • Models, Molecular
  • Mannosyltransferases
  • Humans
  • Glycosyltransferases
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Bacterial
  • Animals, Genetically Modified