Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis.
Cobertura |
England |
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Data(s) |
05/01/2016
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Resumo |
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. |
Formato |
10175 - ? |
Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/26729507 ncomms10175 Nat Commun, 2016, 7 pp. 10175 - ? http://hdl.handle.net/10161/11564 2041-1723 |
Idioma(s) |
ENG |
Relação |
Nat Commun 10.1038/ncomms10175 |
Tipo |
Journal Article |
Palavras-Chave | #Animals #Animals, Genetically Modified #Gene Expression Regulation, Bacterial #Gene Expression Regulation, Enzymologic #Glycosyltransferases #Humans #Mannosyltransferases #Models, Molecular #Protein Conformation #Synechocystis #Zebrafish |