4.7 Article

Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control

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SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/srep20575

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资金

  1. Okazaki ORION project
  2. Ministry of Education, Culture, Sports, Science and Technology, Japan [24770102, 25121730, 15H02491, 25102008, 24249002]
  3. PRESTO project from the Japan Science and Technology Agency [13417569]
  4. Grants-in-Aid for Scientific Research [24770102, 15H02491, 25102001, 15K17889, 25102008] Funding Source: KAKEN

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The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. Glucosidase II catalyzes two-step hydrolysis at alpha 1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. Here we determined the crystal structures of the catalytic alpha subunit of glucosidase II (GII alpha) complexed with two different glucosyl ligands containing the scissile bonds of first-and second-step reactions. Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme.

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