8ZUH

Crystal structure of bovine Fbs2/Skp1/Man3GlcNAc2 complex

Summary for 8ZUH

• Entry DOI: 10.2210/pdb8zuh/pdb
• Descriptor: F-box only protein 6, S-phase kinase-associated protein 1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: ubiquitin, scf, fbs2, ligase complex, ligase
• Biological source: Bos taurus (cattle); More
• Total number of polymer chains: 3
• Total formula weight: 82406.44

Authors

Satoh, T.,Mizushima, T.,Yagi, H.,Kato, R.,Kato, K. (deposition date: 2024-06-09, release date: 2024-09-04, Last modification date: 2024-10-09)

Primary citation

Satoh, T.,Yagi-Utsumi, M.,Ishii, N.,Mizushima, T.,Yagi, H.,Kato, R.,Tachida, Y.,Tateno, H.,Matsuo, I.,Kato, K.,Suzuki, T.,Yoshida, Y.
Structural basis of sugar recognition by SCF FBS2 ubiquitin ligase involved in NGLY1 deficiency.
Febs Lett., 598:2259-2268, 2024

PubMed Abstract: The cytosolic peptide:N-glycanase (PNGase) is involved in the quality control of N-glycoproteins via the endoplasmic reticulum-associated degradation (ERAD) pathway. Mutations in the gene encoding cytosolic PNGase (NGLY1 in humans) cause NGLY1 deficiency. Recent findings indicate that the F-box protein FBS2 of the SCF ubiquitin ligase complex can be a promising drug target for NGLY1 deficiency. Here, we determined the crystal structure of bovine FBS2 complexed with the adaptor protein SKP1 and a sugar ligand, ManGlcNAc, which corresponds to the core pentasaccharide of N-glycan. Our crystallographic data together with NMR data revealed the structural basis of disparate sugar-binding specificities in homologous FBS proteins and identified a potential druggable pocket for in silico docking studies. Our results provide a potential basis for the development of selective inhibitors against FBS2 in NGLY1 deficiency.

PubMed: 39171510
DOI: 10.1002/1873-3468.15003

Experimental method

X-RAY DIFFRACTION (3.2 Å)