Structural Aspects of ER Glycoprotein Quality-Control System Mediated by Glucose Tagging
N-linked oligosaccharides attached to proteins act as tags for glycoprotein quality control, ensuring their appropriate folding and trafficking in cells. Interactions with a variety of intracellular lectins determine glycoprotein fates. Monoglucosylated glycoforms are the hallmarks of incompletely folded glycoproteins in the protein quality-control system, in which glucosidase II and UDP-glucose/glycoprotein glucosyltransferase are, respectively, responsible for glucose trimming and attachment. In this review, we summarize a recently emerging view of the structural basis of the functional mechanisms of these key enzymes as well as substrate N-linked oligosaccharides exhibiting flexible structures, as revealed by applying a series of biophysical techniques including small-angle X-ray scattering, X-ray crystallography, high-speed atomic force microscopy, electron microscopy, and computational simulation in conjunction with NMR spectroscopy.
KeywordsEndoplasmic reticulum Glucose Glucosidase Glucosyltransferase N-linked oligosaccharide Protein quality control
This work was supported in part by the Okazaki ORION project and Grants-in-Aid for Scientific Research (Grant Numbers JP25121730 to T.S., and JP25102008, JP24249002 to K.K.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, the PRESTO project (Grant Number JPMJPR13L5 to T.S.) from the Japan Science and Technology Agency, and by Grant-in-Aid for Research in Nagoya City University.
- Caramelo JJ, Castro OA, Alonso LG, De Prat-Gay G, Parodi AJ (2003) UDP-Glc:glycoprotein glucosyltransferase recognizes structured and solvent accessible hydrophobic patches in molten globule-like folding intermediates. Proc Natl Acad Sci U S A 100:86–91. https://doi.org/10.1073/pnas.262661199 CrossRefPubMedGoogle Scholar
- Kamiya Y, Yanagi K, Kitajima T, Yamaguchi T, Chiba Y, Kato K (2013) Application of metabolic C labeling in conjunction with high-field nuclear magnetic resonance spectroscopy for comparative conformational analysis of high mannose-type oligosaccharides. Biomol Ther 3:108–123. https://doi.org/10.3390/biom3010108 CrossRefGoogle Scholar
- Kornfeld R, Kornfeld S (1985) Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem 54:631–664. https://doi.org/10.1146/annurev.bi.54.070185.003215 CrossRefPubMedGoogle Scholar
- Olson LJ et al (2013) Structure of the lectin mannose 6-phosphate receptor homology (MRH) domain of glucosidase II, an enzyme that regulates glycoprotein folding quality control in the endoplasmic reticulum. J Biol Chem 288:16460–16475. https://doi.org/10.1074/jbc.M113.450239 CrossRefPubMedPubMedCentralGoogle Scholar
- Olson LJ, Orsi R, Peterson FC, Parodi AJ, Kim JJ, D’Alessio C, Dahms NM (2015) Crystal structure and functional analyses of the lectin domain of Glucosidase II: insights into oligomannose recognition. Biochemistry 54:4097–4111. https://doi.org/10.1021/acs.biochem.5b00256 CrossRefPubMedPubMedCentralGoogle Scholar
- Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, Rose DR (2008) Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. J Mol Biol 375:782–792. https://doi.org/10.1016/j.jmb.2007.10.069 CrossRefPubMedGoogle Scholar
- Stanley P, Schachter H, Taniguchi N (2009) N-glycans. In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME (eds) Essentials of Glycobiology. Cold Spring Harbor, Cold Spring Harbor LabGoogle Scholar
- Trombetta ES, Simons JF, Helenius A (1996) Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, conserved from yeast to mammals, and a tightly bound noncatalytic HDEL-containing subunit. J Biol Chem 271:27509–27516. https://doi.org/10.1074/jbc.271.44.27509 CrossRefPubMedGoogle Scholar
- Yamaguchi T, Kato K (2014) Paramagnetism-assisted nuclear magnetic resonance analysis of dynamic conformations and interactions of oligosaccharides glycoscience. In: Taniguchi N, Endo T, Hart GW, Seeberger P, Wong C-H (eds) Biology and medicine. Springer (Japan) in press, https://doi.org/10.1007/978-4-431-54836-2_101-1 Google Scholar
- Zhu T, Satoh T, Kato K (2014) Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. Sci Rep 4:7322. https://doi.org/10.1038/srep07322 CrossRefPubMedPubMedCentralGoogle Scholar