Molecular genetic analysis of the glycosyltransferase fringe in Drosophila

Trudy Correia, Venizelos Papayannopoulos, Vladislav Panin, Pamela Woronoff, Jin Jiang, Thomas F. Vogt, Kenneth D. Irvine

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Fringe proteins are β1,3-N-acetylglucosaminyltransferases that modulate signaling through Notch receptors by modifying O-linked fucose on epidermal growth factor domains. Fringe is highly conserved, and comparison among 18 different Fringe proteins from 11 different species identifies a core set of 84 amino acids that are identical among all Fringes. Fringe is only distantly related to other glycosyltransferases, but analysis of the predicted Drosophila proteome identifies a set of four sequence motifs shared among Fringe and other putative β1,3-glycosyltransferases. To gain functional insight into these conserved sequences, we genetically and molecularly characterized 14 point mutations in Drosophila fringe. Most nonsense mutations act as recessive antimorphs, raising the possibility that Fringe may function as a dimer. Missense mutations identify two distinct motifs that are conserved among β1,3-glycosyltransferases, and that can be modeled onto key motifs in the crystallographic structures of bovine β1,4-galactosyltransferase 1 and human glucuronyltransferase I. Other missense mutations map to amino acids that are conserved among Fringe proteins, but not among other glycosyltransferases, and thus may identify structural motifs that are required for unique aspects of Fringe activity.

Original languageEnglish (US)
Pages (from-to)6404-6409
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number11
DOIs
StatePublished - May 27 2003

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Glycosyltransferases
Drosophila
Molecular Biology
Missense Mutation
N-Acetylglucosaminyltransferases
Notch Receptors
Galactosyltransferases
Amino Acids
Proteins
Fucose
Conserved Sequence
Nonsense Codon
Proteome
Point Mutation
Epidermal Growth Factor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Molecular genetic analysis of the glycosyltransferase fringe in Drosophila. / Correia, Trudy; Papayannopoulos, Venizelos; Panin, Vladislav; Woronoff, Pamela; Jiang, Jin; Vogt, Thomas F.; Irvine, Kenneth D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 11, 27.05.2003, p. 6404-6409.

Research output: Contribution to journalArticle

Correia, Trudy ; Papayannopoulos, Venizelos ; Panin, Vladislav ; Woronoff, Pamela ; Jiang, Jin ; Vogt, Thomas F. ; Irvine, Kenneth D. / Molecular genetic analysis of the glycosyltransferase fringe in Drosophila. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 11. pp. 6404-6409.
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