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- Title
Structural basis of sugar-recognizing ubiquitin ligase.
- Authors
Mizushima, Tsunehiro; Hirao, Takeshi; Yoshida, Yukiko; Lee, Soo Jae; Chiba, Tomoki; Iwai, Kazuhiro; Yamaguchi, Yoshiki; Kato, Koichi; Tsukihara, Tomitake; Tanaka, Keiji
- Abstract
SCF(Fbs1) is a ubiquitin ligase that functions in the endoplasmic reticulum (ER)-associated degradation pathway. Fbs1/Fbx2, a member of the F-box proteins, recognizes high-mannose oligosaccharides. Efficient binding to an N-glycan requires di-N-acetylchitobiose (chitobiose). Here we report the crystal structures of the sugar-binding domain (SBD) of Fbs1 alone and in complex with chitobiose. The SBD is composed of a ten-stranded antiparallel beta-sandwich. The structure of the SBD-chitobiose complex includes hydrogen bonds between Fbs1 and chitobiose and insertion of the methyl group of chitobiose into a small hydrophobic pocket of Fbs1. Moreover, NMR spectroscopy has demonstrated that the amino acid residues adjoining the chitobiose-binding site interact with the outer branches of the carbohydrate moiety. Considering that the innermost chitobiose moieties in N-glycans are usually involved in intramolecular interactions with the polypeptide moieties, we propose that Fbs1 interacts with the chitobiose in unfolded N-glycoprotein, pointing the protein moiety toward E2 for ubiquitination.
- Publication
Nature structural & molecular biology, 2004, Vol 11, Issue 4, p365
- ISSN
1545-9993
- Publication type
Journal Article
- DOI
10.1038/nsmb732