Structural insights into the Notch-modifying glycosyltransferase Fringe.
Fringe proteins are beta1,3-N-acetylglucosaminyltransferases that modify Notch receptors, altering their ligand-binding specificity to regulate Notch signaling in development. We present the crystal structure of mouse Manic Fringe bound to UDP and manganese. The structure reveals amino acid residues involved in recognition of donor substrates and catalysis, and a putative binding pocket for acceptor substrates. Mutations of several invariant residues in this pocket impair Fringe activity in vivo.
Jinek
Martin
M
European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Chen
Ya-Wen
YW
Clausen
Henrik
H
Cohen
Stephen M
SM
Conti
Elena
E
D000818:Animals; D001665:Binding Sites; D005964:Glucosyltransferases; D016695:Glycosyltransferases / Q000737:chemistry* / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D008274:Magnesium / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D013329:Structure-Activity Relationship; D014530:Uridine Diphosphate / Q000737:chemistry
D011506:Proteins; D051880:Receptors, Notch; D014530:Uridine Diphosphate; D016695:Glycosyltransferases; D005964:Glucosyltransferases; C486343:Mfng protein, mouse; D008274:Magnesium