Emerging Structural Insights into Glycoprotein Quality  Control Coupled with N-Glycan Processing in  the Endoplasmic Reticulum

Satoh, Tadashi; Yamaguchi, Takumi; Kato, Koichi

doi:10.3390/molecules20022475

Cited by 37 publications

(24 citation statements)

References 85 publications

(127 reference statements)

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“…4). These results are qualitatively consistent with previous reports based on chemical shift, J coupling, NOE, and PRE data [55,62,[64][65][66][67][68][69][70] and, furthermore, give quantitative insights into conformational fluctuations of this biologically important class of oligosaccharides [71,72].…”

Section: Exploration Of the Conformational Dynamics Of Oligosaccharidessupporting

confidence: 93%

Paramagnetic NMR probes for characterization of the dynamic conformations and interactions of oligosaccharides

Kato

Yamaguchi

2015

Glycoconj J

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Paramagnetism-assisted nuclear magnetic resonance (NMR) techniques have recently been applied to a wide variety of biomolecular systems, using sophisticated immobilization methods to attach paramagnetic probes, such as spin labels and lanthanide-chelating groups, at specific sites of the target biomolecules. This is also true in the field of carbohydrate NMR spectroscopy. NMR analysis of oligosaccharides is often precluded by peak overlap resulting from the lack of variability of local chemical structures, by the insufficiency of conformational restraints from nuclear Overhauser effect (NOE) data due to low proton density, and moreover, by the inherently flexible nature of carbohydrate chains. Paramagnetic probes attached to the reducing ends of oligosaccharides cause paramagnetic relaxation enhancements (PREs) and/or pseudocontact shifts (PCSs) resolve the peak overlap problem. These spectral perturbations can be sources of long-range atomic distance information, which complements the local conformational information derived from J couplings and NOEs. Furthermore, paramagnetic NMR approaches, in conjunction with computational methods, have opened up possibilities for the description of dynamic conformational ensembles of oligosaccharides in solution. Several applications of paramagnetic NMR techniques are presented to demonstrate their utility for characterizing the conformational dynamics of oligosaccharides and for probing the carbohydrate-recognition modes of proteins. These techniques can be applied to the characterization of transient, non-stoichiometric interactions and will contribute to the visualization of dynamic biomolecular processes involving sugar chains.

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Section: Exploration Of the Conformational Dynamics Of Oligosaccharidessupporting

confidence: 93%

Paramagnetic NMR probes for characterization of the dynamic conformations and interactions of oligosaccharides

Kato

Yamaguchi

2015

Glycoconj J

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“…The key role of this glucosylation/deglucosylation cycle in protein folding is now well established (63,71,(869)(870)(871)(872)(873)(874)(875)(876)(877)(878). However, even after the last glucose residue has been permanently removed, there are further steps of recognition of the oligomannose type N-glycans that have been partially processed by ER mannosidases (879)(880)(881)(882)(883)(884). These recognition events are mediated in part by mannose 6-phosphate receptor homology domains in several chaperone proteins, as well as additional mannosidase-like proteins and recognition complexes (130,879,(881)(882)(883)(884)(885)(886)(887)(888).…”

Section: Intracellular Glycoprotein Folding and Degradationmentioning

confidence: 99%

“…However, even after the last glucose residue has been permanently removed, there are further steps of recognition of the oligomannose type N-glycans that have been partially processed by ER mannosidases (879)(880)(881)(882)(883)(884). These recognition events are mediated in part by mannose 6-phosphate receptor homology domains in several chaperone proteins, as well as additional mannosidase-like proteins and recognition complexes (130,879,(881)(882)(883)(884)(885)(886)(887)(888). Effectively, a byzantine array of glycan-modifying and glycan-recognizing proteins determines the final fate of a glycoprotein molecule in the ER--whether it will be allowed to go forward into the Golgi pathway towards its final destination, or be consigned for ERAD.…”

Section: Intracellular Glycoprotein Folding and Degradationmentioning

confidence: 99%

Biological roles of glycans

2016

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Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences.

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“…In eukaryotes, N-glycosylation starts with assembly of a lipidlinked oligosaccharide (LLO) precursor, Glc 3 Man 9 GlcNAc 2pyrophosphate-dolichol (Glc 3 Man 9 Gn 2 -PDol), on the endoplasmic reticulum membrane (1)(2)(3). Addition of the 14 LLO sugars is carried out sequentially by 12 different asparagine-linked glycosylation (Alg) glycosyltransferases (GTase) (4)(5)(6).…”

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confidence: 99%

Alternative routes for synthesis of N‐linked glycans by Alg2 mannosyltransferase

Wang

et al. 2018

FASEB j.

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Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor GlcManGlcNAc-pyrophosphate-dolichol (GlcManGn-PDol) on the endoplasmic reticulum. The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc-PDol to form the trimannosyl core ManGlcNAc-PDol. The biochemical properties of Alg2 are controversial and remain undefined. In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2. Alg2-dependent ManGlcNAc-PDol production relied on net-neutral lipids with a propensity to form bilayers. We further showed addition of the α1,3- and α1,6-mannose can occur independently in either order but at differing rates. The conserved C-terminal EXE motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo. These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D. Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.

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Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum

Cited by 37 publications

References 85 publications

Paramagnetic NMR probes for characterization of the dynamic conformations and interactions of oligosaccharides

Paramagnetic NMR probes for characterization of the dynamic conformations and interactions of oligosaccharides

Biological roles of glycans

Alternative routes for synthesis of N‐linked glycans by Alg2 mannosyltransferase

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