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Updated: Jul 20, 2026
05:48
Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
Structural insights into the Notch-modifying glycosyltransferase Fringe
Martin Jinek1, Ya-Wen Chen, Henrik Clausen
1European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Nature Structural & Molecular Biology
|September 12, 2006
Summary
Fringe proteins modify Notch receptors to regulate development. This study reveals the crystal structure of Manic Fringe, identifying key residues for its enzymatic activity and substrate binding.
Area of Science:
- Biochemistry
- Structural Biology
- Developmental Biology
Background:
- Fringe proteins are beta1,3-N-acetylglucosaminyltransferases.
- They modify Notch receptors, altering ligand-binding specificity.
- This modification regulates Notch signaling during development.
Purpose of the Study:
- To determine the crystal structure of mouse Manic Fringe.
- To identify residues involved in substrate recognition and catalysis.
- To understand the mechanism of Fringe-mediated Notch signaling regulation.
Main Methods:
- X-ray crystallography was used to obtain the structure of mouse Manic Fringe.
- The structure was determined in complex with UDP and manganese.
- Mutagenesis studies were performed to assess the in vivo activity of mutant Fringe proteins.
Main Results:
- The crystal structure of mouse Manic Fringe bound to UDP and manganese was determined.
- Key amino acid residues involved in donor substrate recognition and catalysis were identified.
- A putative binding pocket for acceptor substrates was revealed, with mutations in invariant residues impairing Fringe activity.
Conclusions:
- The structure provides insights into the catalytic mechanism of Fringe proteins.
- Understanding Manic Fringe structure and function is crucial for deciphering Notch signaling pathways.
- This work lays the foundation for further studies on Fringe-glycoprotein interactions.
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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