1UMH

Structural basis of sugar-recognizing ubiquitin ligase

Summary for 1UMH

• Entry DOI: 10.2210/pdb1umh/pdb
• Related: 1UMI
• Descriptor: F-box only protein 2, NICKEL (II) ION (3 entities in total)
• Functional Keywords: ubiquitin, scf, ubiquitin ligase, lectin, riken structural genomics/proteomics initiative, rsgi, structural genomics, ligase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm: Q80UW2
• Total number of polymer chains: 1
• Total formula weight: 21079.70

Authors

Mizushima, T.,Hirao, T.,Yoshida, Y.,Lee, S.J.,Chiba, T.,Iwai, K.,Yamaguchi, Y.,Kato, K.,Tsukihara, T.,Tanaka, K.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2003-10-01, release date: 2004-04-06, Last modification date: 2023-12-27)

Primary citation

Mizushima, T.,Hirao, T.,Yoshida, Y.,Lee, S.J.,Chiba, T.,Iwai, K.,Yamaguchi, Y.,Kato, K.,Tsukihara, T.,Tanaka, K.
Structural basis of sugar-recognizing ubiquitin ligase
NAT.STRUCT.MOL.BIOL., 11:365-370, 2004

PubMed 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.

PubMed: 14990996
DOI: 10.1038/nsmb732

Experimental method

X-RAY DIFFRACTION (2 Å)