Deciphering the Roles of Glycan Processing in Glycoprotein Quality Control through Organic Synthesis

Ito, Yukishige; Takeda, Yoichi

doi:10.1271/bbb.130594

Cited by 3 publications

(3 citation statements)

References 63 publications

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“…The release from this ERQC cycle by glucosidase II catalysed deglucosylation could result in immediate clearance and, therefore, almost undetectable levels of SUBEX-C57Y with only Man 7 GlcNAc 2 N -glycans. Alternatively, demannosylation on the B- and C-branches could reduce the reactivity of glucosidase II leading to higher amounts of monoglucosylated N -glycans on the misfolded protein that is subjected to degradation [ 48 ]. The distinct mannose removal from N -glycans can also provide a mechanism to prolong the interaction of incompletely folded monoglucosylated proteins with CNX/CRT and consequently to an increased chance of proper folding [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

A context-independent N-glycan signal targets the misfolded extracellular domain of Arabidopsis STRUBBELIG to endoplasmic-reticulum-associated degradation

Hüttner

Veit

Vavra

et al. 2014

Biochemical Journal

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N-glycosylation of proteins plays an important role in the determination of the fate of newly synthesized glycoproteins in the endoplasmic reticulum (ER). Specific oligosaccharide structures recruit molecular chaperones that promote folding or mannose-binding lectins that assist in the clearance of improperly-folded glycoproteins by delivery to ER-associated degradation (ERAD). In plants, the mechanisms and factors that recognize non-native proteins and sort them to ERAD are poorly understood. In the present study, we provide evidence that a misfolded variant of the STRUBBELIG (SUB) extracellular domain (SUBEX-C57Y) is degraded in a glycan-dependent manner in plants. SUBEX-C57Y is an ER-retained glycoprotein with three N-glycans that is stabilized in the presence of kifunensine, a potent inhibitor of α-mannosidases. Stable expression in Arabidopsis thaliana knockout mutants revealed that SUBEX-C57Y degradation is dependent on the ER lectin OS9 and its associated ERAD factor SEL1L. SUBEX-C57Y was also stabilized in plants lacking the α-mannosidases MNS4 and MNS5 that generate a terminal α1,6-linked mannose on the C-branch of N-glycans. Notably, the glycan signal for degradation is not constrained to a specific position within SUBEX-C57Y. Structural analysis revealed that SUBEX-C57Y harbours considerable amounts of Glc1Man7GlcNAc2 N-glycans suggesting that the ER-quality control processes involving calnexin/calreticulin (CNX/CRT) and ERAD are tightly interconnected to promote protein folding or disposal by termination of futile folding attempts.

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Section: Discussionmentioning

confidence: 99%

A context-independent N-glycan signal targets the misfolded extracellular domain of Arabidopsis STRUBBELIG to endoplasmic-reticulum-associated degradation

Hüttner

Veit

Vavra

et al. 2014

Biochemical Journal

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“…The latter is the strongest inhibitor and its effect can be even comparable with those of such powerful inhibitors of glucosidases as castanospermine and deoxynojirimycin. By preventing the formation of monoglucosylated glycoproteins the end products are supposed to regu late the entry of newly synthesized glycoproteins into the calnexin/ calreticulin cycle [32,33].…”

Section: Er-associated Protein Degradation (Erad) Releases Glucosylatmentioning

confidence: 99%

“…UGGT has a strong affinity for the core of N-glycans -Man 3 GlcNAc 2 and cannot recognize the oligosaccharides without core GlcNAc 2 . Only the simultaneous recognition of a misfolded part of a protein and an appropriate high-mannose structure of a glycan leads to conformational changes of the enzyme and an addition of a glucose residue to A arm of the oligosaccharide allowing aberrant molecules to become the subjects of the calnexin/ calreticulin cycle again, but proper folded and/or assembled glycoproteins to escape the UGGT activity and proceed to their final destinations through the second reaction of α-GII, α-mannosidase I activity and the Golgi processing [33,34].…”

Section: Er-associated Protein Degradation (Erad) Releases Glucosylatmentioning

confidence: 99%

“Three sources and three component parts” of free oligosaccharides

Pismenetskaya¹,

Butters²

2014

Ukr.Biochem.J.

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abbreviations: BiP -immunoglobulin heavy-chain-binding protein; Derlin -degradation in endoplasmic reticulum protein; DnaJ -heat shock proteins with J-domain; EDEM -ER-degradation enhancing alpha-mannosidase like protein; ENGase -endo-β-N-acetylglucosaminidase; ERAD (ER-associated degradation) -endoplasmic reticulum-associated degradation; ERp57, ERp59, ERp72, ERp44 -disulfide-isomerase like proteins in ER; α-GII -α-glycosidase II; GM1, GM2 -monosialotetrahexosyl-gangliosides; GRP78 -glucose regulated protein; HPLC -high performance liquid chromatography; Hsp70, Hsp40 -heat shock proteins; MALDI-TOF MS -matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry; MAN1B1 (endomannosidase I) -α(1

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Towards the cell-free expression of glycoproteins

Exley¹

2017

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Deciphering the Roles of Glycan Processing in Glycoprotein Quality Control through Organic Synthesis

Cited by 3 publications

References 63 publications

A context-independent N-glycan signal targets the misfolded extracellular domain of Arabidopsis STRUBBELIG to endoplasmic-reticulum-associated degradation

A context-independent N-glycan signal targets the misfolded extracellular domain of Arabidopsis STRUBBELIG to endoplasmic-reticulum-associated degradation

“Three sources and three component parts” of free oligosaccharides

Towards the cell-free expression of glycoproteins

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