title: Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control.
abstract: 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 α1,3-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 α subunit of glucosidase II (GIIα) 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.
authors: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.|JST, PRESTO, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors: Tadashi
authors: T
authors: Satoh
authors: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.|Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
authors: Takayasu
authors: T
authors: Toshimori
authors: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.|Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.|School of Physical Sciences, SOKENDAI (The Graduate University for Advanced Studies), 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
authors: Gengwei
authors: G
authors: Yan
authors: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.|Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.|School of Physical Sciences, SOKENDAI (The Graduate University for Advanced Studies), 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
authors: Takumi
authors: T
authors: Yamaguchi
authors: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.|Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.|School of Physical Sciences, SOKENDAI (The Graduate University for Advanced Studies), 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
authors: Koichi
authors: K
authors: Kato
mesh_terms: D002597:Chaetomium / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008358:Mannose / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D013379:Substrate Specificity; D000520:alpha-Glucosidases / Q000737:chemistry*
chemical_list: D005656:Fungal Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; C034251:4-nitrophenyl-alpha-glucosidase; D000520:alpha-Glucosidases; D005947:Glucose; D008358:Mannose