title: Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase.
abstract: The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. Although FBG3, another F-box protein, shares 51% sequence identity with Fbs1, FBG3 does not bind glycoproteins. To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. The substrate-binding pocket of this model exhibits structural features that differ from those of Fsb1.
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nishio
authors.affiliation: Ubiquitin Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan.
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; C485508:FBXO2 protein, human; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D044843:SKP Cullin F-Box Protein Ligases
keywords: F-box protein; Fbs1; SCF E3 ubiquitin ligase; glycoproteins; sequence–structure relationship