The Structure of Calnexin, an ER Chaperone Involved in Quality Control of Protein Folding

Schrag, Joseph D.; Bergeron, John J.M.; Li, Yunge; Borisova, S.N.; Hahn, Michael G.; Thomas, David Y.; Cygler, Mirosław

doi:10.1016/s1097-2765(01)00318-5

Cited by 361 publications

(337 citation statements)

References 53 publications

(2 reference statements)

Supporting

Mentioning

327

Contrasting

Unclassified

Order By: Relevance

“…Because Trichomonas has a predicted N-glycan precursor (Man 5 GlcNAc 2 ) that lacks Glc (Table 1 and (Fig. 4A) (2, 7).…”

Section: N-glycan-dependent Qc Of Glycoprotein Folding Is Functional Inmentioning

confidence: 99%

“…Fifth and finally, the Saccharomyces UGGT ortholog (Kre5) is deeply divergent (SI Fig. 9), so that it no longer glucosylates In the absence of UDP-Glc the predominant product was NYT-hex 5, whereas in the presence of UDP-Glc the predominant products were NYT-hex 5 and NYT-hex6. (B) HPLC analysis of enzymatic digestion of the latter products showed NYT-hex 5 was Man 5GlcNAc2 and NYT-hex6 was GlcMan5GlcNAc2.…”

Section: Argument For the Secondary Loss Of N-glycan-dependent Qc Ofmentioning

confidence: 99%

See 1 more Smart Citation

The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation

Banerjee

Vishwanath

Cui

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

133

142

View full text Add to dashboard Cite

Asn-linked glycans (N-glycans) play important roles in the quality control (QC) of glycoprotein folding in the endoplasmic reticulum (ER) lumen and in ER-associated degradation (ERAD) of proteins by cytosolic proteasomes. A UDP-Glc:glycoprotein glucosyltransferase glucosylates N-glycans of misfolded proteins, which are then bound and refolded by calreticulin and/or calnexin in association with a protein disulfide isomerase. Alternatively, an ␣-1,2-mannosidase (Mns1) and mannosidase-like proteins (ER degradation-enhancing ␣-mannosidase-like proteins 1, 2, and 3) are part of a process that results in the dislocation of misfolded glycoproteins into the cytosol, where proteins are degraded in the proteasome. Recently we found that numerous protists and fungi contain 0 -11 sugars in their N-glycan precursors versus 14 sugars in those of animals, plants, fungi, and Dictyostelium. Our goal here was to determine what effect N-glycan precursor diversity has on N-glycan-dependent QC systems of glycoprotein folding and ERAD. N-glycan-dependent QC of folding (UDP-Glc:glycoprotein glucosyltransferase, calreticulin, and/or calnexin) was present and active in some but not all protists containing at least five mannose residues in their N-glycans and was absent in protists lacking Man. In contrast, N-glycan-dependent ERAD appeared to be absent from the majority of protists. However, Trypanosoma and Trichomonas genomes predicted ER degradation-enhancing ␣-mannosidase-like protein and Mns1 orthologs, respectively, each of which had ␣-mannosidase activity in vitro. Phylogenetic analyses suggested that the diversity of N-glycan-dependent QC of glycoprotein folding (and possibly that of ERAD) was best explained by secondary loss. We conclude that N-glycan precursor length has profound effects on N-glycan-dependent QC of glycoprotein folding and ERAD.protein folding ͉ protists ͉ Trichomonas ͉ Entamoeba

show abstract

“…Because Trichomonas has a predicted N-glycan precursor (Man 5 GlcNAc 2 ) that lacks Glc (Table 1 and (Fig. 4A) (2, 7).…”

Section: N-glycan-dependent Qc Of Glycoprotein Folding Is Functional Inmentioning

confidence: 99%

Section: Argument For the Secondary Loss Of N-glycan-dependent Qc Ofmentioning

confidence: 99%

The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation

Banerjee

Vishwanath

Cui

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

133

142

View full text Add to dashboard Cite

show abstract

“…For the chaperone probe, we selected Crt for several reasons: the availability of a knockout cell line (19), chemical inhibitors of its function (20), well characterized biochemical properties (21)(22)(23)(24)(25)(26), and structural information (24,(27)(28)(29). Based on this information, we generated a GFP-tagged Crt (Crt-GFP) (Fig.…”

mentioning

confidence: 99%

Monitoring chaperone engagement of substrates in the endoplasmic reticulum of live cells

Snapp

Sharma

Lippincott‐Schwartz

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

112

116

View full text Add to dashboard Cite

The folding environment in the endoplasmic reticulum (ER) depends on multiple abundant chaperones that function together to accommodate a range of substrates. The ways in which substrate engagement shapes either specific chaperone dynamics or general ER attributes in vivo remain unknown. In this study, we have evaluated how changes in substrate flux through the ER influence the diffusion of both the lectin chaperone calreticulin and an inert reporter of ER crowdedness. During acute changes in substrate load, the inert probe revealed no changes in ER organization, despite significant changes in calreticulin dynamics. By contrast, inhibition of the lectin chaperone system caused rapid changes in the ER environment that could be reversed over time by easing new substrate burden. Our findings provide insight into the normal organization and dynamics of an ER chaperone and characterize the capacity of the ER to maintain homeostasis during acute changes in chaperone activity and availability.castanospermine ͉ fluorescence loss in photobleaching ͉ fluorescence recovery after photobleaching ͉ pactamycin ͉ puromycin

show abstract

“…From the recently solved three-dimensional structures of the CRT P-domain and the luminal domain of CNX (24,25), it was revealed that both chaperones contain a globular lectin domain with a long, protruding arm-like extension, referred to as the P-domain. The site of interaction with ERp57 has been mapped to the outermost tip of the P-domain in both CNX and CRT (26 -28).…”

mentioning

confidence: 99%

ERp57 Is a Multifunctional Thiol-Disulfide Oxidoreductase

Frickel

Frei

Bouvier

et al. 2004

Journal of Biological Chemistry

179

129

View full text Add to dashboard Cite

The thiol-disulfide oxidoreductase ERp57 is a soluble protein of the endoplasmic reticulum and the closest known homologue of protein disulfide isomerase. The protein interacts with the two lectin chaperones calnexin and calreticulin and thereby promotes the oxidative folding of newly synthesized glycoproteins. Here we have characterized several fundamental structural and functional properties of ERp57 in vitro, such as the domain organization, shape, redox potential, and the ability to catalyze different thiol-disulfide exchange reactions. Like protein disulfide isomerase, we find ERp57 to be comprised of four structural domains. The protein has an elongated shape of 3.4 ؎ 0.1 nm in diameter and 16.8 ؎ 0.5 nm in length. The two redox-active a and a domains were determined to have redox potentials of ؊0.167 and ؊0.156 V, respectively. Furthermore, ERp57 was shown to efficiently catalyze disulfide reduction, disulfide isomerization, and dithiol oxidation in substrate proteins. The implications of these findings for the function of the protein in vivo are discussed.

show abstract

The Structure of Calnexin, an ER Chaperone Involved in Quality Control of Protein Folding

Cited by 361 publications

References 53 publications

The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation

The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation

Monitoring chaperone engagement of substrates in the endoplasmic reticulum of live cells

ERp57 Is a Multifunctional Thiol-Disulfide Oxidoreductase

Contact Info

Product

Resources

About