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PMID: 15665075 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The diversity of dolichol-linked precursors to Asn-linked glycans likely results from secondary loss of sets of glycosyltransferases.

Samuelson J, Banerjee S, Magnelli P, Cui J, Kelleher DJ, Gilmore R, Robbins PW

Abstract

The vast majority of eukaryotes (fungi, plants, animals, slime mold, and euglena) synthesize Asn-linked glycans (Alg) by means of a lipid-linked precursor dolichol-PP-GlcNAc2Man9Glc3. Knowledge of this pathway is important because defects in the glycosyltransferases (Alg1-Alg12 and others not yet identified), which make dolichol-PP-glycans, lead to numerous congenital disorders of glycosylation. Here we used bioinformatic and experimental methods to characterize Alg glycosyltransferases and dolichol-PP-glycans of diverse protists, including many human pathogens, with the following major conclusions. First, it is demonstrated that common ancestry is a useful method of predicting the Alg glycosyltransferase inventory of each eukaryote. Second, in the vast majority of cases, this inventory accurately predicts the dolichol-PP-glycans observed. Third, Alg glycosyltransferases are missing in sets from each organism (e.g., all of the glycosyltransferases that add glucose and mannose are absent from Giardia and Plasmodium). Fourth, dolichol-PP-GlcNAc2Man5 (present in Entamoeba and Trichomonas) and dolichol-PP- and N-linked GlcNAc2 (present in Giardia) have not been identified previously in wild-type organisms. Finally, the present diversity of protist and fungal dolichol-PP-linked glycans appears to result from secondary loss of glycosyltransferases from a common ancestor that contained the complete set of Alg glycosyltransferases.

MeSH Terms
Animals Asparagine Bacteria/enzymology,genetics Computational Biology Dolichols/metabolism Evolution, Molecular Genetic Variation Glycopeptides/biosynthesis Glycosyltransferases/genetics,metabolism Humans Polysaccharides/chemistry Species Specificity
Chemicals
Dolichols Glycopeptides Polysaccharides Asparagine Glycosyltransferases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Samuelson John
Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 715 Albany Street, Boston, MA 02118-2932, USA. [email protected]
Banerjee Sulagna
Magnelli Paula
Cui Jike
Kelleher Daniel J
Gilmore Reid
Robbins Phillips W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2005-02-01
Epub
2005-00-21
Pages
1548-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC545090
Subset
IM
Grants
NIGMS NIH HHS · GM31318 · United States
NIGMS NIH HHS · R01 GM043768 · United States
NIGMS NIH HHS · R01 GM031318 · United States
NIAID NIH HHS · AI44070 · United States
NIGMS NIH HHS · GM43768 · United States
NIAID NIH HHS · AI48082 · United States
NIAID NIH HHS · R01 AI048082 · United States
NIAID NIH HHS · R01 AI044070 · United States
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