title: Effects of N-glycan precursor length diversity on quality control of protein folding and on protein glycosylation.
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 (Glc3Man9GlcNAc2), protist N-glycan precursors vary from Glc3Man9GlcNAc2 (Acanthamoeba) to Man9GlcNAc2 (Trypanosoma) to Glc3Man5GlcNAc2 (Toxoplasma) to Man5GlcNAc2 (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 Man5GlcNAc2 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*).
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 72 East Concord St, Evans 425, Boston, MA 02118, USA. Electronic address: jsamuels@bu.edu.
authors.forename: John
authors.initials: J
authors.lastname: Samuelson
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 72 East Concord St, Evans 425, Boston, MA 02118, USA. Electronic address: robbinspw2@gmail.com.
authors.forename: Phillips W
authors.initials: PW
authors.lastname: Robbins
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D056890:Eukaryota / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D011134:Polysaccharides; D015800:Protozoan Proteins
keywords: ER-associated degradation; Endoplasmic reticulum; Evolution; N-glycan precursors; Parasites; Quality control of protein folding