PDBsum entry 2e33

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protein ligands Protein-protein interface(s) links
Ligase/hydrolase PDB id
Protein chains
175 a.a. *
124 a.a. *
* Residue conservation analysis
PDB id:
Name: Ligase/hydrolase
Title: Structural basis for selection of glycosylated substrate by ubiquitin ligase
Structure: F-box only protein 2. Chain: a. Fragment: residues 105-297. Synonym: fbs1. Engineered: yes. Ribonuclease pancreatic. Chain: b. Synonym: rnase 1, rnase a, ribonuclease b. Ec:
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Bos taurus. Cattle. Organism_taxid: 9913
2.70Å     R-factor:   0.220     R-free:   0.288
Authors: T.Mizushima,Y.Yoshida,T.Kumanomidou,Y.Hasegawa,T.Yamane,K.Ta
Key ref:
T.Mizushima et al. (2007). Structural basis for the selection of glycosylated substrates by SCF(Fbs1) ubiquitin ligase. Proc Natl Acad Sci U S A, 104, 5777-5781. PubMed id: 17389369 DOI: 10.1073/pnas.0610312104
20-Nov-06     Release date:   20-Mar-07    
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Protein chain
Pfam   ArchSchema ?
Q80UW2  (FBX2_MOUSE) -  F-box only protein 2
297 a.a.
175 a.a.*
Protein chain
Pfam   ArchSchema ?
P61823  (RNAS1_BOVIN) -  Ribonuclease pancreatic
150 a.a.
124 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain B: E.C.  - Pancreatic ribonuclease.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     metabolic process   3 terms 
  Biochemical function     nucleic acid binding     6 terms  


DOI no: 10.1073/pnas.0610312104 Proc Natl Acad Sci U S A 104:5777-5781 (2007)
PubMed id: 17389369  
Structural basis for the selection of glycosylated substrates by SCF(Fbs1) ubiquitin ligase.
T.Mizushima, Y.Yoshida, T.Kumanomidou, Y.Hasegawa, A.Suzuki, T.Yamane, K.Tanaka.
The ubiquitin ligase complex SCF(Fbs1), which contributes to the ubiquitination of glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. In SCF ubiquitin ligases, a diverse array of F-box proteins confers substrate specificity. Fbs1/Fbx2, a member of the F-box protein family, recognizes high-mannose oligosaccharides. To elucidate the structural basis of SCF(Fbs1) function, we determined the crystal structures of the Skp1-Fbs1 complex and the sugar-binding domain (SBD) of the Fbs1-glycoprotein complex. The mechanistic model indicated by the structures appears to be well conserved among the SCF ubiquitin ligases. The structure of the SBD-glycoprotein complex indicates that the SBD primarily recognizes Man(3)GlcNAc(2), thereby explaining the broad activity of the enzyme against various glycoproteins. Comparison of two crystal structures of the Skp1-Fbs1 complex revealed the relative motion of a linker segment between the F-box and the SBD domains, which might underlie the ability of the complex to recognize different acceptor lysine residues for ubiquitination.
  Selected figure(s)  
Figure 4.
Fig. 4. Regulatory mechanism of SCF^Fbs1 glycoprotein ubiquitination. (A) Comparison of the two crystal structures of the Skp1–Fbs1 complex. Skp1 (form 1), Fbs1 (form 1), Skp1 (form 2), and Fbs1 (form 2) are blue, red, yellow, and green, respectively. (B) Schematic representation of the model for ubiquitination on SCF^Fbs1. The E2 active-site cysteine and acceptor lysine residues are depicted with circled letters.
Figure 5.
Fig. 5. Model of the SCF^Fbs1–RNaseB complex bound to E2. Cul1, Rbx1, Skp1, Fbs1, RNaseB, and E2 are green, orange, blue, red, cyan, and yellow, respectively. Lysine residues on the RNaseB surface are presented in ball-and-stick format and are coral.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21288713 D.M.Duda, D.C.Scott, M.F.Calabrese, E.S.Zimmerman, N.Zheng, and B.A.Schulman (2011).
Structural regulation of cullin-RING ubiquitin ligase complexes.
  Curr Opin Struct Biol, 21, 257-264.  
20152160 E.Sakata, T.Satoh, S.Yamamoto, Y.Yamaguchi, M.Yagi-Utsumi, E.Kurimoto, K.Tanaka, S.Wakatsuki, and K.Kato (2010).
Crystal structure of UbcH5b~ubiquitin intermediate: insight into the formation of the self-assembled E2~Ub conjugates.
  Structure, 18, 138-147.
PDB code: 3a33
20083119 J.Liu, and R.Nussinov (2010).
Molecular dynamics reveal the essential role of linker motions in the function of cullin-RING E3 ligases.
  J Mol Biol, 396, 1508-1523.  
19798438 J.Liu, and R.Nussinov (2009).
The mechanism of ubiquitination in the cullin-RING E3 ligase machinery: conformational control of substrate orientation.
  PLoS Comput Biol, 5, e1000527.  
18203720 K.A.Glenn, R.F.Nelson, H.M.Wen, A.J.Mallinger, and H.L.Paulson (2008).
Diversity in tissue expression, substrate binding, and SCF complex formation for a lectin family of ubiquitin ligases.
  J Biol Chem, 283, 12717-12729.  
18698327 T.Ravid, and M.Hochstrasser (2008).
Diversity of degradation signals in the ubiquitin-proteasome system.
  Nat Rev Mol Cell Biol, 9, 679-690.  
17933515 P.Knipscheer, and T.K.Sixma (2007).
Protein-protein interactions regulate Ubl conjugation.
  Curr Opin Struct Biol, 17, 665-673.  
17986767 Y.Yoshida (2007).
F-box proteins that contain sugar-binding domains.
  Biosci Biotechnol Biochem, 71, 2623-2631.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.