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PMID: 28530709 Published · ppublish English Journal Article

Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1.

Nature chemical biology ·Vol. 13 ·No. 7 ·2017-07-00 ·Pages 757-763

Li Z, Han K, Pak JE, Satkunarajah M, Zhou D, Rini JM

Abstract

Protein O-fucosyltransferase 1 (POFUT1) fucosylates the epidermal growth factor (EGF)-like domains found in cell-surface and secreted glycoproteins including Notch and its ligands. Although Notch fucosylation is critical for development, and POFUT1 deficiency leads to human disease, how this enzyme binds and catalyzes the fucosylation of its diverse EGF-like domain substrates has not been determined. Reported here is the X-ray crystal structure of mouse POFUT1 in complex with several EGF-like domains, including EGF12 and EGF26 of Notch. Overall shape complementarity, interactions with invariant atoms of the fucosylation motif and flexible segments on POFUT1 all define its EGF-like-domain binding properties. Using large-scale structural and sequence analysis, we also show that POFUT1 binds EGF-like domains of the hEGF type and that the highly correlated presence of POFUT1 and fucosylatable hEGFs has accompanied animal evolution.

MeSH Terms
Animals Crystallography, X-Ray Epidermal Growth Factor/chemistry Fucosyltransferases/metabolism Humans Mice Models, Molecular Protein Domains Receptors, Notch/metabolism
Chemicals
Receptors, Notch Epidermal Growth Factor Fucosyltransferases Pofut1 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Li Zhijie ORCID
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada. | Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Han Kristina
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
Pak John E
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Satkunarajah Malathy
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada. | Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Zhou Dongxia
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada. | Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Rini James M
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada. | Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
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Article Info
Journal
Nature chemical biology
Abbr.
Nat Chem Biol
ISSN
1552-4469
DOI
10.1038/nchembio.2381
Published
2017-07-00
Epub
2017-00-22
Pages
757-763
Language
English
Region
United States
NLM ID
101231976
Subset
IM
External Links
PubMed source DOI: 10.1038/nchembio.2381 View journal details
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