Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis.
| dc.contributor.author | Ardiccioni, Chiara | |
| dc.contributor.author | Clarke, Oliver B | |
| dc.contributor.author | Tomasek, David | |
| dc.contributor.author | Issa, Habon A | |
| dc.contributor.author | von Alpen, Desiree C | |
| dc.contributor.author | Pond, Heather L | |
| dc.contributor.author | Banerjee, Surajit | |
| dc.contributor.author | Rajashankar, Kanagalaghatta R | |
| dc.contributor.author | Liu, Qun | |
| dc.contributor.author | Guan, Ziqiang | |
| dc.contributor.author | Li, Chijun | |
| dc.contributor.author | Kloss, Brian | |
| dc.contributor.author | Bruni, Renato | |
| dc.contributor.author | Kloppmann, Edda | |
| dc.contributor.author | Rost, Burkhard | |
| dc.contributor.author | Manzini, M Chiara | |
| dc.contributor.author | Shapiro, Lawrence | |
| dc.contributor.author | Mancia, Filippo | |
| dc.coverage.spatial | England | |
| dc.date.accessioned | 2016-02-01T14:21:47Z | |
| dc.date.issued | 2016-01-05 | |
| dc.description.abstract | 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. | |
| dc.identifier | ||
| dc.identifier | ncomms10175 | |
| dc.identifier.eissn | 2041-1723 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | Nat Commun | |
| dc.relation.isversionof | 10.1038/ncomms10175 | |
| dc.subject | Animals | |
| dc.subject | Animals, Genetically Modified | |
| dc.subject | Gene Expression Regulation, Bacterial | |
| dc.subject | Gene Expression Regulation, Enzymologic | |
| dc.subject | Glycosyltransferases | |
| dc.subject | Humans | |
| dc.subject | Mannosyltransferases | |
| dc.subject | Models, Molecular | |
| dc.subject | Protein Conformation | |
| dc.subject | Synechocystis | |
| dc.subject | Zebrafish | |
| dc.title | Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Guan, Ziqiang|0000-0002-8082-3423 | |
| pubs.author-url | ||
| pubs.begin-page | 10175 | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Biochemistry | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.publication-status | Published online | |
| pubs.volume | 7 |
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