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PDBsum entry 2fid
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protein metals Protein-protein interface(s) links
Protein turnover/endocytosis PDB id
2fid

 

 

 

 

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Contents
Protein chains
73 a.a. *
60 a.a. *
Metals
_ZN
Waters ×2
* Residue conservation analysis
PDB id:
2fid
Name: Protein turnover/endocytosis
Title: Crystal structure of a bovine rabex-5 fragment complexed with ubiquitin
Structure: Ubiquitin. Chain: a. Rab5 gdp/gtp exchange factor. Chain: b. Fragment: a20 zinc finger and inverted ubiquitin interacting motif domains. Synonym: rabex-5. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: rabgef1, rabex5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
2.80Å     R-factor:   0.217     R-free:   0.268
Authors: S.Lee,J.H.Hurley
Key ref:
S.Lee et al. (2006). Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5. Nat Struct Mol Biol, 13, 264-271. PubMed id: 16462746 DOI: 10.1038/nsmb1064
Date:
29-Dec-05     Release date:   07-Feb-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0CH28  (UBC_BOVIN) -  Polyubiquitin-C from Bos taurus
Seq:
Struc: 		 
Seq:
Struc: 		690 a.a.
73 a.a.
Protein chain
Pfam   ArchSchema ?
O18973  (RABX5_BOVIN) -  Rab5 GDP/GTP exchange factor from Bos taurus
Seq:
Struc: 		492 a.a.
60 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1038/nsmb1064 Nat Struct Mol Biol 13:264-271 (2006)
PubMed id: 16462746  
 
 
Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5.
S.Lee, Y.C.Tsai, R.Mattera, W.J.Smith, M.S.Kostelansky, A.M.Weissman, J.S.Bonifacino, J.H.Hurley.
 
  ABSTRACT  
 
Rabex-5 is an exchange factor for Rab5, a master regulator of endosomal trafficking. Rabex-5 binds monoubiquitin, undergoes covalent ubiquitination and contains an intrinsic ubiquitin ligase activity, all of which require an N-terminal A20 zinc finger followed immediately by a helix. The structure of the N-terminal portion of Rabex-5 bound to ubiquitin at 2.5-A resolution shows that Rabex-5-ubiquitin interactions occur at two sites. The first site is a new type of ubiquitin-binding domain, an inverted ubiquitin-interacting motif, which binds with approximately 29-microM affinity to the canonical Ile44 hydrophobic patch on ubiquitin. The second is a diaromatic patch on the A20 zinc finger, which binds with approximately 22-microM affinity to a polar region centered on Asp58 of ubiquitin. The A20 zinc-finger diaromatic patch mediates ubiquitin-ligase activity by directly recruiting a ubiquitin-loaded ubiquitin-conjugating enzyme.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structure of the Rabex-5 A20 ZnF domain and IUIM. (a) The domain structures of Rabex-5 and the construct used in this study. Magenta, ZnF domain; green, IUIM; HB, helical bundle; Vps9, Vps9-homology domain; CC, coiled coil; PR, proline-rich. (b) Rabex-5 (ribbon) contacts ubiquitin (orange and blue surfaces) at two sites in the crystal lattice. (c) Superposition of the four crystallographically independent molecules of the A20 ZnF domain and IUIM. Green, P6[1] molecule; pink, magenta and red, the three independent molecules in the asymmetric unit of the C2 lattice. (d) The zinc-binding site in the A20 ZnF domain. Orange, sulfurs of cysteine side chains; red sphere, zinc. (e) Ribbon and stick representation showing exposed hydrophobic side chains. (f) Surface of the A20 ZnF domain and IUIM colored by residue type: green, hydrophobic; red, acidic; blue, basic; white, uncharged polar; yellow, cysteine. 		Figure 2.
Figure 2. Ubiquitin recognition by Rabex-5. (a) Ubiquitin (beige ribbon and stick model) bound to Rabex-5 IUIM (green surface model). (b) Rabex-5 IUIM (green ribbon and sticks) bound to ubiquitin (orange surface). (c) Ubiquitin (blue ribbon and sticks) bound to Rabex-5 A20 ZnF domain (magenta surface). (d) Rabex-5 A20 ZnF domain (magenta ribbon and sticks) bound to ubiquitin (blue surface). (e) Ubiquitin binds Rabex-5 through two different nonoverlapping surfaces on ubiquitin. Orange, surfaces contacting the IUIM; blue, surfaces contacting the A20 ZnF.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 264-271) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22286100 N.V.Dimova, N.A.Hathaway, B.H.Lee, D.S.Kirkpatrick, M.L.Berkowitz, S.P.Gygi, D.Finley, and R.W.King (2012).
APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1.
  Nat Cell Biol, 14, 168-176.  
21857666 A.Plechanovová, E.G.Jaffray, S.A.McMahon, K.A.Johnson, I.Navrátilová, J.H.Naismith, and R.T.Hay (2011).
Mechanism of ubiquitylation by dimeric RING ligase RNF4.
  Nat Struct Mol Biol, 18, 1052-1059.
PDB code: 2xeu
21293909 M.Kang, M.Fokar, H.Abdelmageed, and R.D.Allen (2011).
Arabidopsis SAP5 functions as a positive regulator of stress responses and exhibits E3 ubiquitin ligase activity.
  Plant Mol Biol, 75, 451-466.  
19939937 C.T.Archer, and T.Kodadek (2010).
The hydrophobic patch of ubiquitin is required to protect transactivator-promoter complexes from destabilization by the proteasomal ATPases.
  Nucleic Acids Res, 38, 789-796.  
20655224 H.Yan, M.Jahanshahi, E.A.Horvath, H.Y.Liu, and C.M.Pfleger (2010).
Rabex-5 ubiquitin ligase activity restricts Ras signaling to establish pathway homeostasis in Drosophila.
  Curr Biol, 20, 1378-1382.  
21095585 I.Bosanac, I.E.Wertz, B.Pan, C.Yu, S.Kusam, C.Lam, L.Phu, Q.Phung, B.Maurer, D.Arnott, D.S.Kirkpatrick, V.M.Dixit, and S.G.Hymowitz (2010).
Ubiquitin binding to A20 ZnF4 is required for modulation of NF-κB signaling.
  Mol Cell, 40, 548-557.
PDB codes: 3oj3 3oj4
19893571 I.E.Wertz, and V.M.Dixit (2010).
Regulation of death receptor signaling by the ubiquitin system.
  Cell Death Differ, 17, 14-24.  
20692608 J.Colicelli (2010).
Signal transduction: RABGEF1 fingers RAS for ubiquitination.
  Curr Biol, 20, R630-R632.  
20655225 L.Xu, V.Lubkov, L.J.Taylor, and D.Bar-Sagi (2010).
Feedback regulation of Ras signaling by Rabex-5-mediated ubiquitination.
  Curr Biol, 20, 1372-1377.  
20159559 M.G.Bomar, S.D'Souza, M.Bienko, I.Dikic, G.C.Walker, and P.Zhou (2010).
Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1.
  Mol Cell, 37, 408-417.
PDB code: 2khu
  20543575 N.Shembade, and E.Harhaj (2010).
A20 inhibition of NFκB and inflammation: targeting E2:E3 ubiquitin enzyme complexes.
  Cell Cycle, 9, 2481-2482.  
20383180 S.G.Hymowitz, and I.E.Wertz (2010).
A20: from ubiquitin editing to tumour suppression.
  Nat Rev Cancer, 10, 332-341.  
19763089 E.Laplantine, E.Fontan, J.Chiaravalli, T.Lopez, G.Lakisic, M.Véron, F.Agou, and A.Israël (2009).
NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain.
  EMBO J, 28, 2885-2895.  
19033441 F.Cordier, O.Grubisha, F.Traincard, M.Véron, M.Delepierre, and F.Agou (2009).
The Zinc Finger of NEMO Is a Functional Ubiquitin-binding Domain.
  J Biol Chem, 284, 2902-2907.  
20064473 H.B.Kamadurai, J.Souphron, D.C.Scott, D.M.Duda, D.J.Miller, D.Stringer, R.C.Piper, and B.A.Schulman (2009).
Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex.
  Mol Cell, 36, 1095-1102.
PDB codes: 3jvz 3jw0
19773779 I.Dikic, S.Wakatsuki, and K.J.Walters (2009).
Ubiquitin-binding domains - from structures to functions.
  Nat Rev Mol Cell Biol, 10, 659-671.  
19423704 Q.S.Fu, C.J.Zhou, H.C.Gao, Y.J.Jiang, Z.R.Zhou, J.Hong, W.M.Yao, A.X.Song, D.H.Lin, and H.Y.Hu (2009).
Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2-activating Protein.
  J Biol Chem, 284, 19043-19052.
PDB codes: 2k89 2k8a 2k8b 2k8c
19500350 S.Pinato, C.Scandiuzzi, N.Arnaudo, E.Citterio, G.Gaudino, and L.Penengo (2009).
RNF168, a new RING finger, MIU-containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX.
  BMC Mol Biol, 10, 55.  
19183301 Y.Zwang, and Y.Yarden (2009).
Systems biology of growth factor-induced receptor endocytosis.
  Traffic, 10, 349-363.  
18515172 I.E.Wertz, and V.M.Dixit (2008).
Ubiquitin-mediated regulation of TNFR1 signaling.
  Cytokine Growth Factor Rev, 19, 313-324.  
18523727 N.A.Lakomek, K.F.Walter, C.Farès, O.F.Lange, B.L.de Groot, H.Grubmüller, R.Brüschweiler, A.Munk, S.Becker, J.Meiler, and C.Griesinger (2008).
Self-consistent residual dipolar coupling based model-free analysis for the robust determination of nanosecond to microsecond protein dynamics.
  J Biomol NMR, 41, 139-155.  
18342009 O.Hitotsumatsu, R.C.Ahmad, R.Tavares, M.Wang, D.Philpott, E.E.Turer, B.L.Lee, N.Shiffin, R.Advincula, B.A.Malynn, C.Werts, and A.Ma (2008).
The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals.
  Immunity, 28, 381-390.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18497827 P.Schreiner, X.Chen, K.Husnjak, L.Randles, N.Zhang, S.Elsasser, D.Finley, I.Dikic, K.J.Walters, and M.Groll (2008).
Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction.
  Nature, 453, 548-552.
PDB codes: 2r2y 2z59
18772883 R.Mattera, and J.S.Bonifacino (2008).
Ubiquitin binding and conjugation regulate the recruitment of Rabex-5 to early endosomes.
  EMBO J, 27, 2484-2494.  
18270205 T.E.Messick, N.S.Russell, A.J.Iwata, K.L.Sarachan, R.Shiekhattar, J.R.Shanks, F.E.Reyes-Turcu, K.D.Wilkinson, and R.Marmorstein (2008).
Structural basis for ubiquitin recognition by the Otu1 ovarian tumor domain protein.
  J Biol Chem, 283, 11038-11049.
PDB codes: 3by4 3c0r
18205020 V.Kanneganti, and A.K.Gupta (2008).
Overexpression of OsiSAP8, a member of stress associated protein (SAP) gene family of rice confers tolerance to salt, drought and cold stress in transgenic tobacco and rice.
  Plant Mol Biol, 66, 445-462.  
18819927 Y.Amemiya, P.Azmi, and A.Seth (2008).
Autoubiquitination of BCA2 RING E3 ligase regulates its own stability and affects cell migration.
  Mol Cancer Res, 6, 1385-1396.  
17496917 A.Adhikari, M.Xu, and Z.J.Chen (2007).
Ubiquitin-mediated activation of TAK1 and IKK.
  Oncogene, 26, 3214-3226.  
17450153 A.Delprato, and D.G.Lambright (2007).
Structural basis for Rab GTPase activation by VPS9 domain exchange factors.
  Nat Struct Mol Biol, 14, 406-412.
PDB code: 2ot3
17477837 B.T.Dye, and B.A.Schulman (2007).
Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins.
  Annu Rev Biophys Biomol Struct, 36, 131-150.  
17235285 C.Ottmann, L.Yasmin, M.Weyand, J.L.Veesenmeyer, M.H.Diaz, R.H.Palmer, M.S.Francis, A.R.Hauser, A.Wittinghofer, and B.Hallberg (2007).
Phosphorylation-independent interaction between 14-3-3 and exoenzyme S: from structure to pathogenesis.
  EMBO J, 26, 902-913.
PDB code: 2o02
17699593 H.Zhu, G.Zhu, J.Liu, Z.Liang, X.C.Zhang, and G.Li (2007).
Rabaptin-5-independent membrane targeting and Rab5 activation by Rabex-5 in the cell.
  Mol Biol Cell, 18, 4119-4128.  
17341663 J.Kalesnikoff, E.J.Rios, C.C.Chen, M.Alejandro Barbieri, M.Tsai, S.Y.Tam, and S.J.Galli (2007).
Roles of RabGEF1/Rabex-5 domains in regulating Fc epsilon RI surface expression and Fc epsilon RI-dependent responses in mast cells.
  Blood, 109, 5308-5317.  
17304240 M.G.Bomar, M.T.Pai, S.R.Tzeng, S.S.Li, and P.Zhou (2007).
Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta.
  EMBO Rep, 8, 247-251.
PDB code: 2i5o
17442384 M.S.Kostelansky, C.Schluter, Y.Y.Tam, S.Lee, R.Ghirlando, B.Beach, E.Conibear, and J.H.Hurley (2007).
Molecular architecture and functional model of the complete yeast ESCRT-I heterotetramer.
  Cell, 129, 485-498.
PDB code: 2p22
17512543 M.T.Pai, S.R.Tzeng, J.J.Kovacs, M.A.Keaton, S.S.Li, T.P.Yao, and P.Zhou (2007).
Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin.
  J Mol Biol, 370, 290-302.
PDB code: 2i50
17679095 P.Peschard, G.Kozlov, T.Lin, I.A.Mirza, A.M.Berghuis, S.Lipkowitz, M.Park, and K.Gehring (2007).
Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b.
  Mol Cell, 27, 474-485.
PDB codes: 2ooa 2oob
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
17355622 T.Woelk, S.Sigismund, L.Penengo, and S.Polo (2007).
The ubiquitination code: a signalling problem.
  Cell Div, 2, 11.  
17303403 V.Kirkin, and I.Dikic (2007).
Role of ubiquitin- and Ubl-binding proteins in cell signaling.
  Curr Opin Cell Biol, 19, 199-205.  
16901703 C.Raiborg, T.Slagsvold, and H.Stenmark (2006).
A new side to ubiquitin.
  Trends Biochem Sci, 31, 541-544.  
16564012 F.E.Reyes-Turcu, J.R.Horton, J.E.Mullally, A.Heroux, X.Cheng, and K.D.Wilkinson (2006).
The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin.
  Cell, 124, 1197-1208.
PDB codes: 2g43 2g45
16564007 J.W.Harper, and B.A.Schulman (2006).
Structural complexity in ubiquitin recognition.
  Cell, 124, 1133-1136.  
16803894 K.Tashiro, H.Konishi, E.Sano, H.Nabeshi, E.Yamauchi, and H.Taniguchi (2006).
Suppression of the ligand-mediated down-regulation of epidermal growth factor receptor by Ymer, a novel tyrosine-phosphorylated and ubiquitinated protein.
  J Biol Chem, 281, 24612-24622.  
16499958 L.Penengo, M.Mapelli, A.G.Murachelli, S.Confalonieri, L.Magri, A.Musacchio, P.P.Di Fiore, S.Polo, and T.R.Schneider (2006).
Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.
  Cell, 124, 1183-1195.
PDB codes: 2c7m 2c7n
16518384 S.L.Alam, and W.I.Sundquist (2006).
Two new structures of Ub-receptor complexes. U2.
  Nat Struct Mol Biol, 13, 186-188.  
17033811 S.Vij, and A.K.Tyagi (2006).
Genome-wide analysis of the stress associated protein (SAP) gene family containing A20/AN1 zinc-finger(s) in rice and their phylogenetic relationship with Arabidopsis.
  Mol Genet Genomics, 276, 565-575.  
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.

 

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