The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation
Authors
Banerjee, SulagnaVishwanath, Prashanth
Cui, Jike
Kelleher, Daniel J.
Gilmore, Reid
Robbins, Phillips W.
Samuelson, John
Document Type
Journal ArticlePublication Date
2007-07-10Keywords
AnimalsCarbohydrate Sequence
Endoplasmic Reticulum
Entamoeba histolytica
*Evolution, Molecular
Glycoproteins
Mannosidases
Molecular Sequence Data
Plasmodium falciparum
Polysaccharides
Predictive Value of Tests
Proteasome Endopeptidase Complex
*Protein Folding
Protozoan Proteins
Saccharomyces cerevisiae Proteins
Trichomonas
Biochemistry
Biochemistry, Biophysics, and Structural Biology
Molecular Biology
Metadata
Show full item recordAbstract
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 alpha-1,2-mannosidase (Mns1) and mannosidase-like proteins (ER degradation-enhancing alpha-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 alpha-mannosidase-like protein and Mns1 orthologs, respectively, each of which had alpha-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.Source
Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11676-81. Epub 2007 Jul 2. Link to article on publisher's siteDOI
10.1073/pnas.0704862104Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26043PubMed ID
17606910Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.0704862104