Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum
In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc3Man9GlcNAc2). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. In these...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-01-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/20/2/2475 |
| _version_ | 1819018366039359488 |
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| author | Tadashi Satoh Takumi Yamaguchi Koichi Kato |
| author_facet | Tadashi Satoh Takumi Yamaguchi Koichi Kato |
| author_sort | Tadashi Satoh |
| collection | DOAJ |
| description | In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc3Man9GlcNAc2). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. In these processes, the transiently expressed N-glycans, as processing intermediates, function as signals for the determination of glycoprotein fates, i.e., folding, transport, or degradation through interactions of a series of intracellular lectins. The monoglucosylated glycoforms are hallmarks of incompletely folded states of glycoproteins in this system, whereas the outer mannose trimming leads to ER-associated glycoprotein degradation. This review outlines the recently emerging evidence regarding the molecular and structural basis of this glycoprotein quality control system, which is regulated through dynamic interplay among intracellular lectins, glycosidases, and glycosyltransferase. Structural snapshots of carbohydrate-lectin interactions have been provided at the atomic level using X-ray crystallographic analyses. Conformational ensembles of uncomplexed triantennary high-mannose-type oligosaccharides have been characterized in a quantitative manner using molecular dynamics simulation in conjunction with nuclear magnetic resonance spectroscopy. These complementary views provide new insights into glycoprotein recognition in quality control coupled with N-glycan processing. |
| first_indexed | 2024-12-21T03:18:16Z |
| format | Article |
| id | doaj.art-5b169e31caf8454183a3ba1b00f5b65b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T03:18:16Z |
| publishDate | 2015-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5b169e31caf8454183a3ba1b00f5b65b2022-12-21T19:17:46ZengMDPI AGMolecules1420-30492015-01-012022475249110.3390/molecules20022475molecules20022475Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic ReticulumTadashi Satoh0Takumi Yamaguchi1Koichi Kato2Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanGraduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanGraduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanIn the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc3Man9GlcNAc2). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. In these processes, the transiently expressed N-glycans, as processing intermediates, function as signals for the determination of glycoprotein fates, i.e., folding, transport, or degradation through interactions of a series of intracellular lectins. The monoglucosylated glycoforms are hallmarks of incompletely folded states of glycoproteins in this system, whereas the outer mannose trimming leads to ER-associated glycoprotein degradation. This review outlines the recently emerging evidence regarding the molecular and structural basis of this glycoprotein quality control system, which is regulated through dynamic interplay among intracellular lectins, glycosidases, and glycosyltransferase. Structural snapshots of carbohydrate-lectin interactions have been provided at the atomic level using X-ray crystallographic analyses. Conformational ensembles of uncomplexed triantennary high-mannose-type oligosaccharides have been characterized in a quantitative manner using molecular dynamics simulation in conjunction with nuclear magnetic resonance spectroscopy. These complementary views provide new insights into glycoprotein recognition in quality control coupled with N-glycan processing.http://www.mdpi.com/1420-3049/20/2/2475calnexin/calreticulin cyclecargo receptorendoplasmic reticulumintracellular lectinN-glycan processingNMR spectroscopyglycoprotein quality controlX-ray crystallography |
| spellingShingle | Tadashi Satoh Takumi Yamaguchi Koichi Kato Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum Molecules calnexin/calreticulin cycle cargo receptor endoplasmic reticulum intracellular lectin N-glycan processing NMR spectroscopy glycoprotein quality control X-ray crystallography |
| title | Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum |
| title_full | Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum |
| title_fullStr | Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum |
| title_full_unstemmed | Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum |
| title_short | Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum |
| title_sort | emerging structural insights into glycoprotein quality control coupled with n glycan processing in the endoplasmic reticulum |
| topic | calnexin/calreticulin cycle cargo receptor endoplasmic reticulum intracellular lectin N-glycan processing NMR spectroscopy glycoprotein quality control X-ray crystallography |
| url | http://www.mdpi.com/1420-3049/20/2/2475 |
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