PDBsum entry 2j59

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
(+ 0 more) 165 a.a. *
(+ 0 more) 113 a.a. *
GTP ×6
DIO ×3
EDO ×3
SO4 ×6
_MG ×6
Waters ×1656
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of the arf1:arhgap21-arfbd complex
Structure: Adp-ribosylation factor 1. Chain: a, b, c, d, e, f. Fragment: delta 17-arf1, residues 17-180. Synonym: arf1. Engineered: yes. Mutation: yes. Rho-gtpase activating protein 10. Chain: m, n, o, p, q, r. Fragment: arf-binding domain, residues 929-1096.
Source: Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Expression_system_taxid: 562
2.10Å     R-factor:   0.209     R-free:   0.243
Authors: J.Menetrey,M.Perderiset,J.Cicolari,T.Dubois,N.El Khatib, F.El Khadali,M.Franco,P.Chavrier,A.Houdusse
Key ref:
J.Ménétrey et al. (2007). Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi membranes. EMBO J, 26, 1953-1962. PubMed id: 17347647 DOI: 10.1038/sj.emboj.7601634
13-Sep-06     Release date:   20-Feb-07    
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Protein chains
Pfam   ArchSchema ?
P84078  (ARF1_MOUSE) -  ADP-ribosylation factor 1
181 a.a.
165 a.a.*
Protein chains
Pfam   ArchSchema ?
Q5T5U3  (RHG21_HUMAN) -  Rho GTPase-activating protein 21
1957 a.a.
113 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     synapse   15 terms 
  Biological process     dendritic spine organization   10 terms 
  Biochemical function     nucleotide binding     5 terms  


DOI no: 10.1038/sj.emboj.7601634 EMBO J 26:1953-1962 (2007)
PubMed id: 17347647  
Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi membranes.
J.Ménétrey, M.Perderiset, J.Cicolari, T.Dubois, N.Elkhatib, F.El Khadali, M.Franco, P.Chavrier, A.Houdusse.
ARHGAP21 is a Rho family GTPase-activating protein (RhoGAP) that controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. ARHGAP21 is recruited to the Golgi by binding to another small GTPase, ARF1. Here, we present the crystal structure of the activated GTP-bound form of ARF1 in a complex with the Arf-binding domain (ArfBD) of ARHGAP21 at 2.1 A resolution. We show that ArfBD comprises a PH domain adjoining a C-terminal alpha helix, and that ARF1 interacts with both of these structural motifs through its switch regions and triggers structural rearrangement of the PH domain. We used site-directed mutagenesis to confirm that both the PH domain and the helical motif are essential for the binding of ArfBD to ARF1 and for its recruitment to the Golgi. Our data demonstrate that two well-known small GTPase-binding motifs, the PH domain and the alpha helical motif, can combine to create a novel mode of binding to Arfs.
  Selected figure(s)  
Figure 1.
Figure 1 Structure of the ARF1:ArfBD complex. (A) A cartoon diagram of the ARF1:ArfBD complex is shown in two distinct orientations. ARF1 is shown in grey with the 1 helix and switch I region in light and dark blue, respectively, the interswitch region in green and the switch II region in red. The Mg.GTP ligand is shown as a grey stick model. ArfBD is shown in white with its 5' region ( 5' strand plus 5'– 6' loop) in pink, the 1' helix in orange and the Cter helix in yellow. Tyr999 and Ile1053 of ArfBD are shown as stick models. The two adjacent contact areas of the ARF1:ArfBD complex interface are delineated by black boxes on the right-hand view. (B) Detailed view of the interface between the Cter helix and the PH domain of ArfBD. (C–F) Detailed views of the ARF1:ArfBD interface. The secondary structures are shown as ribbons and the residues as sticks. Hydrogen bonds are indicated by dashed lines. (C) The 5' region of ArfBD (pink) lies between the interswitch (green) and switch I (blue) regions of ARF1 centred on Tyr999. (D) The network of water-mediated interactions made between Asp996 of the 5' region (in pink) of ArfBD and ARF1. (E) The switch I (blue) region of ARF1 interacts with the 5' region (pink) and the 1' helix (orange) of ArfBD. (F) The Cter helix (yellow) of ArfBD is grasped between the switch II (red) and the interswitch/switch I (green/blue) regions of ARF1.
Figure 2.
Figure 2 The hydrophobic pocket and triad patch of Arf proteins. (A) Front-view of the ARF1 hydrophobic pocket (transparent grey area) and the hydrophobic triad patch (transparent purple area) with the hydrophobic residue side chains shown as stick models. (B) Sequence alignment of the Arf proteins (nomenclature from Kahn et al, 2006) with residues of the hydrophobic pocket indicated with grey shading and those of the triad patch indicated in purple. Residues conserved with ARF1 are shown in bold.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2007, 26, 1953-1962) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21439824 G.Montagnac, Forges, E.Smythe, C.Gueudry, M.Romao, J.Salamero, and P.Chavrier (2011).
Decoupling of activation and effector binding underlies ARF6 priming of fast endocytic recycling.
  Curr Biol, 21, 574-579.  
20442785 E.W.Lamb, C.D.Walls, J.T.Pesce, D.K.Riner, S.K.Maynard, E.T.Crow, T.A.Wynn, B.C.Schaefer, and S.J.Davies (2010).
Blood fluke exploitation of non-cognate CD4+ T cell help to facilitate parasite development.
  PLoS Pathog, 6, e1000892.  
20525016 H.Hehnly, W.Xu, J.L.Chen, and M.Stamnes (2010).
Cdc42 regulates microtubule-dependent Golgi positioning.
  Traffic, 11, 1067-1078.  
20725658 J.Janin (2010).
Protein-protein docking tested in blind predictions: the CAPRI experiment.
  Mol Biosyst, 6, 2351-2362.  
20839234 M.F.Lensink, and S.J.Wodak (2010).
Blind predictions of protein interfaces by docking calculations in CAPRI.
  Proteins, 78, 3085-3095.  
21134634 P.Chavrier, and J.Ménétrey (2010).
Toward a structural understanding of arf family:effector specificity.
  Structure, 18, 1552-1558.  
20597089 S.J.Fleishman, J.E.Corn, E.M.Strauch, T.A.Whitehead, I.Andre, J.Thompson, J.J.Havranek, R.Das, P.Bradley, and D.Baker (2010).
Rosetta in CAPRI rounds 13-19.
  Proteins, 78, 3212-3218.  
20601958 Y.Liu, R.A.Kahn, and J.H.Prestegard (2010).
Dynamic structure of membrane-anchored Arf*GTP.
  Nat Struct Mol Biol, 17, 876-881.
PDB code: 2ksq
19692570 H.Hehnly, K.M.Longhini, J.L.Chen, and M.Stamnes (2009).
Retrograde Shiga toxin trafficking is regulated by ARHGAP21 and Cdc42.
  Mol Biol Cell, 20, 4303-4312.  
19452551 N.Kowalsman, and M.Eisenstein (2009).
Combining interface core and whole interface descriptors in postscan processing of protein-protein docking models.
  Proteins, 77, 297-318.  
19644450 T.Isabet, G.Montagnac, K.Regazzoni, B.Raynal, F.El Khadali, P.England, M.Franco, P.Chavrier, A.Houdusse, and J.Ménétrey (2009).
The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4.
  EMBO J, 28, 2835-2845.
PDB code: 2w83
18973596 L.M.Craveiro, D.Hakkoum, O.Weinmann, L.Montani, L.Stoppini, and M.E.Schwab (2008).
Neutralization of the membrane protein Nogo-A enhances growth and reactive sprouting in established organotypic hippocampal slice cultures.
  Eur J Neurosci, 28, 1808-1824.  
17803214 A.Heifetz, S.Pal, and G.R.Smith (2007).
Protein-protein docking: progress in CAPRI rounds 6-12 using a combination of methods: the introduction of steered solvated molecular dynamics.
  Proteins, 69, 816-822.  
17506703 A.K.Gillingham, and S.Munro (2007).
The small G proteins of the Arf family and their regulators.
  Annu Rev Cell Dev Biol, 23, 579-611.  
17803217 A.May, and M.Zacharias (2007).
Protein-protein docking in CAPRI using ATTRACT to account for global and local flexibility.
  Proteins, 69, 774-780.  
17671979 C.Wang, O.Schueler-Furman, I.Andre, N.London, S.J.Fleishman, P.Bradley, B.Qian, and D.Baker (2007).
RosettaDock in CAPRI rounds 6-12.
  Proteins, 69, 758-763.  
17853449 G.Terashi, M.Takeda-Shitaka, K.Kanou, M.Iwadate, D.Takaya, and H.Umeyama (2007).
The SKE-DOCK server and human teams based on a combined method of shape complementarity and free energy estimation.
  Proteins, 69, 866-872.  
17942688 J.Heuvingh, M.Franco, P.Chavrier, and C.Sykes (2007).
ARF1-mediated actin polymerization produces movement of artificial vesicles.
  Proc Natl Acad Sci U S A, 104, 16928-16933.  
17671980 J.Janin (2007).
The targets of CAPRI rounds 6-12.
  Proteins, 69, 699-703.  
18042453 J.P.DiNitto, A.Delprato, M.T.Gabe Lee, T.C.Cronin, S.Huang, A.Guilherme, M.P.Czech, and D.G.Lambright (2007).
Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors.
  Mol Cell, 28, 569-583.
PDB codes: 2r09 2r0d
17803212 K.Wiehe, B.Pierce, W.W.Tong, H.Hwang, J.Mintseris, and Z.Weng (2007).
The performance of ZDOCK and ZRANK in rounds 6-11 of CAPRI.
  Proteins, 69, 719-725.  
17803211 M.Bueno, and C.J.Camacho (2007).
Acidic groups docked to well defined wetted pockets at the core of the binding interface: a tale of scoring and missing protein interactions in CAPRI.
  Proteins, 69, 786-792.  
17918726 M.F.Lensink, R.Méndez, and S.J.Wodak (2007).
Docking and scoring protein complexes: CAPRI 3rd Edition.
  Proteins, 69, 704-718.  
17671977 M.Król, R.A.Chaleil, A.L.Tournier, and P.A.Bates (2007).
Implicit flexibility in protein docking: cross-docking and local refinement.
  Proteins, 69, 750-757.  
17803216 N.Li, Z.Sun, and F.Jiang (2007).
SOFTDOCK application to protein-protein interaction benchmark and CAPRI.
  Proteins, 69, 801-808.  
17803233 N.London, and O.Schueler-Furman (2007).
Assessing the energy landscape of CAPRI targets by FunHunt.
  Proteins, 69, 809-815.  
17876821 S.Grosdidier, C.Pons, A.Solernou, and J.Fernández-Recio (2007).
Prediction and scoring of docking poses with pyDock.
  Proteins, 69, 852-858.  
17803234 Vries, A.D.van Dijk, M.Krzeminski, M.van Dijk, A.Thureau, V.Hsu, T.Wassenaar, and A.M.Bonvin (2007).
HADDOCK versus HADDOCK: new features and performance of HADDOCK2.0 on the CAPRI targets.
  Proteins, 69, 726-733.  
17876812 S.R.Comeau, D.Kozakov, R.Brenke, Y.Shen, D.Beglov, and S.Vajda (2007).
ClusPro: performance in CAPRI rounds 6-11 and the new server.
  Proteins, 69, 781-785.  
17803223 X.Q.Gong, S.Chang, Q.H.Zhang, C.H.Li, L.Z.Shen, X.H.Ma, M.H.Wang, B.Liu, H.Q.He, W.Z.Chen, and C.X.Wang (2007).
A filter enhanced sampling and combinatorial scoring study for protein docking in CAPRI.
  Proteins, 69, 859-865.  
17853451 Y.Shen, R.Brenke, D.Kozakov, S.R.Comeau, D.Beglov, and S.Vajda (2007).
Docking with PIPER and refinement with SDU in rounds 6-11 of CAPRI.
  Proteins, 69, 734-742.  
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.