Effects of N-glycan precursor length diversity on quality control of protein folding and on protein glycosylation. (May 2015)

• Record Type: Journal Article
• Authors: Samuelson, John; Robbins, Phillips W.
• Is Part Of: Seminars in cell & developmental biology. Volume 41(2015)
• Page Start: 121
• Page End: 128
• Publication Date: 2015-05
• Subjects: CPY Saccharomyces carboxypeptidase Y -- CPY* misfolded CPY mutant -- N-glycan Asn-linked glycan -- PPI peptidylprolyl isomerase -- PDI protein disulfide isomerase -- QC quality control -- UGGT UDP-glucose:glucosyltransferase; Endoplasmic reticulum -- ER-associated degradation -- Evolution -- N-glycan precursors -- Quality control of protein folding -- Parasites; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2014.11.008
• Languages: English
• ISSNs: 1084-9521

Abstract

Abstract: Asparagine-linked glycans ( N -glycans) of medically important protists have much to tell us about the evolution of N -glycosylation and of N -glycan-dependent quality control ( N -glycan QC) of protein folding in the endoplasmic reticulum. While host N -glycans are built upon a dolichol-pyrophosphate-linked precursor with 14 sugars (Glc3 Man9 GlcNAc2 ), protist N -glycan precursors vary from Glc3 Man9 GlcNAc2 ( Acanthamoeba ) to Man9 GlcNAc2 ( Trypanosoma ) to Glc3 Man5 GlcNAc2 ( Toxoplasma ) to Man5 GlcNAc2 ( Entamoeba, Trichomonas, and Eimeria ) to GlcNAc2 ( Plasmodium and Giardia ) to zero ( Theileria ). As related organisms have differing N -glycan lengths (e.g. Toxoplasma, Eimeria, Plasmodium, and Theileria ), the present N -glycan variation is based upon secondary loss of Alg genes, which encode enzymes that add sugars to the N -glycan precursor. An N -glycan precursor with Man5 GlcNAc2 is necessary but not sufficient for N -glycan QC, which is predicted by the presence of the UDP-glucose:glucosyltransferase (UGGT) plus calreticulin and/or calnexin. As many parasites lack glucose in their N -glycan precursor, UGGT product may be identified by inhibition of glucosidase II. The presence of an armless calnexin in Toxoplasma suggests secondary loss of N -glycan QC from coccidia. Positive selection for N -glycan sites occurs in secreted proteins of organisms with N -glycan QC and is based upon an increased likelihood of threonine but not serine in the +2 position versus asparagine. In contrast, there appears to be selection against N -glycan length in Plasmodium and N -glycan site density in Toxoplasma . Finally, there is suggestive evidence for N -glycan-dependent ERAD in Trichomonas, which glycosylates and degrades the exogenous reporter mutant carboxypeptidase Y (CPY*).