PDBsum entry 1ksh

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protein ligands metals Protein-protein interface(s) links
Signaling protein/hydrolase PDB id
Protein chains
165 a.a. *
142 a.a. *
Waters ×124
* Residue conservation analysis
PDB id:
Name: Signaling protein/hydrolase
Title: Complex of arl2 and pde delta, crystal form 2 (native)
Structure: Arf-like protein 2. Chain: a. Engineered: yes. Mutation: yes. Retinal rod rhodopsin-sensitive cgmp 3',5'- cyclic phosphodiesterase delta-subunit. Chain: b. Synonym: gmp-pde delta, p17 protein. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: arl2. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Dimer (from PQS)
1.80Å     R-factor:   0.244     R-free:   0.271
Authors: M.Hanzal-Bayer,L.Renault,P.Roversi,A.Wittinghofer,R.C.Hillig
Key ref:
M.Hanzal-Bayer et al. (2002). The complex of Arl2-GTP and PDE delta: from structure to function. EMBO J, 21, 2095-2106. PubMed id: 11980706 DOI: 10.1093/emboj/21.9.2095
13-Jan-02     Release date:   08-May-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9D0J4  (ARL2_MOUSE) -  ADP-ribosylation factor-like protein 2
184 a.a.
165 a.a.*
Protein chain
Pfam   ArchSchema ?
O43924  (PDE6D_HUMAN) -  Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta
150 a.a.
142 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   13 terms 
  Biological process     tight junction assembly   15 terms 
  Biochemical function     nucleotide binding     8 terms  


DOI no: 10.1093/emboj/21.9.2095 EMBO J 21:2095-2106 (2002)
PubMed id: 11980706  
The complex of Arl2-GTP and PDE delta: from structure to function.
M.Hanzal-Bayer, L.Renault, P.Roversi, A.Wittinghofer, R.C.Hillig.
Arf-like (Arl) proteins are close relatives of the Arf regulators of vesicular transport, but their function is unknown. Here, we present the crystal structure of full-length Arl2-GTP in complex with its effector PDE delta solved in two crystal forms (Protein Data Bank codes 1KSG, 1KSH and 1KSJ). Arl2 shows a dramatic conformational change from the GDP-bound form, which suggests that it is reversibly membrane associated. PDE delta is structurally closely related to RhoGDI and contains a deep empty hydrophobic pocket. Further experiments show that H-Ras, Rheb, Rho6 and G alpha(i1) interact with PDE delta and that, at least for H-Ras, the intact C-terminus is required. We suggest PDE delta to be a specific soluble transport factor for certain prenylated proteins and Arl2-GTP a regulator of PDE delta-mediated transport.
  Selected figure(s)  
Figure 3.
Figure 3 Overall view of Arl2-GTP:PDE and comparison with Rap1A-GppNHp:RafRBD and Cdc42-GDP:RhoGDI. (A) Ribbon diagram of the complex of Arl2-GTP and PDE , with color coding of Arl2 as in Figure 1B. (B) Complex of Rap1A-GppNHp and the Ras binding domain of Raf (Nassar et al., 1995). Color coding as in (A). (C) Complex of Cdc42-GDP and RhoGDI1 (Hoffman et al., 2000). Color coding as in (A). C-terminal geranylgeranyl modification is shown in light blue.
Figure 4.
Figure 4 The interface of Arl2 and PDE . (A) Stereo representation of a view along the interface (Arl2- 2 and PDE - 7). (B) Schematic representation. Color coding as in Figure 3. Interactions as dotted lines. Residues are boxed, water molecules are represented by circles.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 2095-2106) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22179043 A.Chandra, H.E.Grecco, V.Pisupati, D.Perera, L.Cassidy, F.Skoulidis, S.A.Ismail, C.Hedberg, M.Hanzal-Bayer, A.R.Venkitaraman, A.Wittinghofer, and P.I.Bastiaens (2012).
The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins.
  Nat Cell Biol, 14, 148-158.  
22298042 M.R.Philips (2012).
Ras hitchhikes on PDE6δ.
  Nat Cell Biol, 14, 128-129.  
21170023 A.S.Selyunin, S.E.Sutton, B.A.Weigele, L.E.Reddick, R.C.Orchard, S.M.Bresson, D.R.Tomchick, and N.M.Alto (2011).
The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold.
  Nature, 469, 107-111.
PDB codes: 3pcr 3pcs
22108793 C.Kiel, A.Vogt, A.Campagna, A.Chatr-aryamontri, M.Swiatek-de Lange, M.Beer, S.Bolz, A.F.Mack, N.Kinkl, G.Cesareni, L.Serrano, and M.Ueffing (2011).
Structural and functional protein network analyses predict novel signaling functions for rhodopsin.
  Mol Syst Biol, 7, 551.  
21129209 A.F.Neuwald (2010).
Bayesian classification of residues associated with protein functional divergence: Arf and Arf-like GTPases.
  Biol Direct, 5, 66.  
20123908 L.Chen, S.W.Chan, X.Zhang, M.Walsh, C.J.Lim, W.Hong, and H.Song (2010).
Structural basis of YAP recognition by TEAD4 in the hippo pathway.
  Genes Dev, 24, 290-300.
PDB code: 3jua
21081081 P.Bhagatji, R.Leventis, R.Rich, C.J.Lin, and J.R.Silvius (2010).
Multiple cellular proteins modulate the dynamics of K-ras association with the plasma membrane.
  Biophys J, 99, 3327-3335.  
21134634 P.Chavrier, and J.Ménétrey (2010).
Toward a structural understanding of arf family:effector specificity.
  Structure, 18, 1552-1558.  
20368466 W.Tian, J.Yu, D.R.Tomchick, D.Pan, and X.Luo (2010).
Structural and functional analysis of the YAP-binding domain of human TEAD2.
  Proc Natl Acad Sci U S A, 107, 7293-7298.
PDB code: 3l15
20123905 Z.Li, B.Zhao, P.Wang, F.Chen, Z.Dong, H.Yang, K.L.Guan, and Y.Xu (2010).
Structural insights into the YAP and TEAD complex.
  Genes Dev, 24, 235-240.
PDB code: 3kys
18981177 L.K.Bailey, L.J.Campbell, K.A.Evetts, K.Littlefield, E.Rajendra, D.Nietlispach, D.Owen, and H.R.Mott (2009).
The Structure of Binder of Arl2 (BART) Reveals a Novel G Protein Binding Domain: IMPLICATIONS FOR FUNCTION.
  J Biol Chem, 284, 992-999.
PDB code: 2k9a
18846587 M.Alexander, M.Gerauer, M.Pechlivanis, B.Popkirova, R.Dvorsky, L.Brunsveld, H.Waldmann, and J.Kuhlmann (2009).
Mapping the isoprenoid binding pocket of PDEdelta by a semisynthetic, photoactivatable N-Ras lipoprotein.
  Chembiochem, 10, 98.  
19381362 P.Dadvar, M.O'Flaherty, A.Scholten, K.Rumpel, and A.J.Heck (2009).
A chemical proteomics based enrichment technique targeting the interactome of the PDE5 inhibitor PF-4540124.
  Mol Biosyst, 5, 472-482.  
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
19368893 T.Zhang, S.Li, Y.Zhang, C.Zhong, Z.Lai, and J.Ding (2009).
Crystal structure of the ARL2-GTP-BART complex reveals a novel recognition and binding mode of small GTPase with effector.
  Structure, 17, 602-610.
PDB codes: 3doe 3dof
18664567 K.Alpadi, V.G.Magupalli, S.Käppel, L.Köblitz, K.Schwarz, G.M.Seigel, C.H.Sung, and F.Schmitz (2008).
RIBEYE recruits Munc119, a mammalian ortholog of the Caenorhabditis elegans protein unc119, to synaptic ribbons of photoreceptor synapses.
  J Biol Chem, 283, 26461-26467.  
17949773 S.Karan, H.Zhang, S.Li, J.M.Frederick, and W.Baehr (2008).
A model for transport of membrane-associated phototransduction polypeptides in rod and cone photoreceptor inner segments.
  Vision Res, 48, 442-452.  
18376416 S.Veltel, R.Gasper, E.Eisenacher, and A.Wittinghofer (2008).
The retinitis pigmentosa 2 gene product is a GTPase-activating protein for Arf-like 3.
  Nat Struct Mol Biol, 15, 373-380.
PDB codes: 3bh6 3bh7
18674751 V.Cantagrel, J.L.Silhavy, S.L.Bielas, D.Swistun, S.E.Marsh, J.Y.Bertrand, S.Audollent, T.Attié-Bitach, K.R.Holden, W.B.Dobyns, D.Traver, L.Al-Gazali, B.R.Ali, T.H.Lindner, T.Caspary, E.A.Otto, F.Hildebrandt, I.A.Glass, C.V.Logan, C.A.Johnson, C.Bennett, F.Brancati, E.M.Valente, C.G.Woods, and J.G.Gleeson (2008).
Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome.
  Am J Hum Genet, 83, 170-179.  
17962409 A.F.Neuwald (2007).
Galpha Gbetagamma dissociation may be due to retraction of a buried lysine and disruption of an aromatic cluster by a GTP-sensing Arg Trp pair.
  Protein Sci, 16, 2570-2577.  
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.  
17496142 H.Zhang, S.Li, T.Doan, F.Rieke, P.B.Detwiler, J.M.Frederick, and W.Baehr (2007).
Deletion of PrBP/delta impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments.
  Proc Natl Acad Sci U S A, 104, 8857-8862.  
17347647 J.Ménétrey, M.Perderiset, J.Cicolari, T.Dubois, N.Elkhatib, F.El Khadali, M.Franco, P.Chavrier, and A.Houdusse (2007).
Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi membranes.
  EMBO J, 26, 1953-1962.
PDB code: 2j59
16525022 C.Zhou, L.Cunningham, A.I.Marcus, Y.Li, and R.A.Kahn (2006).
Arl2 and Arl3 regulate different microtubule-dependent processes.
  Mol Biol Cell, 17, 2476-2487.  
16527812 S.J.Wilson, and E.M.Smyth (2006).
Internalization and recycling of the human prostacyclin receptor is modulated through its isoprenylation-dependent interaction with the delta subunit of cGMP phosphodiesterase 6.
  J Biol Chem, 281, 11780-11786.  
16691442 U.Ashery, O.Yizhar, B.Rotblat, G.Elad-Sfadia, B.Barkan, R.Haklai, and Y.Kloog (2006).
Spatiotemporal organization of Ras signaling: rasosomes and the galectin switch.
  Cell Mol Neurobiol, 26, 471-495.  
16824054 U.Ashery, O.Yizhar, B.Rotblat, and Y.Kloog (2006).
Nonconventional trafficking of Ras associated with Ras signal organization.
  Traffic, 7, 119-126.  
15504722 A.W.Norton, S.Hosier, J.M.Terew, N.Li, A.Dhingra, N.Vardi, W.Baehr, and R.H.Cote (2005).
Evaluation of the 17-kDa prenyl-binding protein as a regulatory protein for phototransduction in retinal photoreceptors.
  J Biol Chem, 280, 1248-1256.  
16099990 C.J.O'Neal, M.G.Jobling, R.K.Holmes, and W.G.Hol (2005).
Structural basis for the activation of cholera toxin by human ARF6-GTP.
  Science, 309, 1093-1096.
PDB codes: 2a5d 2a5f 2a5g
16027222 J.S.Goodwin, K.R.Drake, C.Rogers, L.Wright, J.Lippincott-Schwartz, M.R.Philips, and A.K.Kenworthy (2005).
Depalmitoylated Ras traffics to and from the Golgi complex via a nonvesicular pathway.
  J Cell Biol, 170, 261-272.  
15933719 M.Wu, T.Wang, E.Loh, W.Hong, and H.Song (2005).
Structural basis for recruitment of RILP by small GTPase Rab7.
  EMBO J, 24, 1491-1501.
PDB codes: 1t91 1yhn
15564045 C.G.Burd, T.I.Strochlic, and S.R.Gangi Setty (2004).
Arf-like GTPases: not so Arf-like after all.
  Trends Cell Biol, 14, 687-694.  
15572774 E.Blanc, P.Roversi, C.Vonrhein, C.Flensburg, S.M.Lea, and G.Bricogne (2004).
Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT.
  Acta Crystallogr D Biol Crystallogr, 60, 2210-2221.  
15036861 E.Pechkova, and C.Nicolini (2004).
Protein nanocrystallography: a new approach to structural proteomics.
  Trends Biotechnol, 22, 117-122.  
15205467 G.Elad-Sfadia, R.Haklai, E.Balan, and Y.Kloog (2004).
Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity.
  J Biol Chem, 279, 34922-34930.  
15507210 H.Sondermann, S.M.Soisson, S.Boykevisch, S.S.Yang, D.Bar-Sagi, and J.Kuriyan (2004).
Structural analysis of autoinhibition in the Ras activator Son of sevenless.
  Cell, 119, 393-405.
PDB codes: 1xd2 1xd4 1xdv
14561760 H.Zhang, X.H.Liu, K.Zhang, C.K.Chen, J.M.Frederick, G.D.Prestwich, and W.Baehr (2004).
Photoreceptor cGMP phosphodiesterase delta subunit (PDEdelta) functions as a prenyl-binding protein.
  J Biol Chem, 279, 407-413.  
14718928 M.Wu, L.Lu, W.Hong, and H.Song (2004).
Structural basis for recruitment of GRIP domain golgin-245 by small GTPase Arl1.
  Nat Struct Mol Biol, 11, 86-94.
PDB code: 1r4a
14580338 B.Panic, O.Perisic, D.B.Veprintsev, R.L.Williams, and S.Munro (2003).
Structural basis for Arl1-dependent targeting of homodimeric GRIP domains to the Golgi apparatus.
  Mol Cell, 12, 863-874.
PDB code: 1upt
14690595 E.Mossessova, R.A.Corpina, and J.Goldberg (2003).
Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism.
  Mol Cell, 12, 1403-1411.
PDB code: 1re0
12767220 G.Zhu, P.Zhai, X.He, S.Terzyan, R.Zhang, A.Joachimiak, J.Tang, and X.C.Zhang (2003).
Crystal structure of the human GGA1 GAT domain.
  Biochemistry, 42, 6392-6399.
PDB code: 1oxz
12728271 J.F.Hancock (2003).
Ras proteins: different signals from different locations.
  Nat Rev Mol Cell Biol, 4, 373-384.  
12912990 J.F.Shern, J.D.Sharer, D.C.Pallas, F.Bartolini, N.J.Cowan, M.S.Reed, J.Pohl, and R.A.Kahn (2003).
Cytosolic Arl2 is complexed with cofactor D and protein phosphatase 2A.
  J Biol Chem, 278, 40829-40836.  
12654246 T.Schwartz, and G.Blobel (2003).
Structural basis for the function of the beta subunit of the eukaryotic signal recognition particle receptor.
  Cell, 112, 793-803.
PDB code: 1nrj
12679809 T.Shiba, M.Kawasaki, H.Takatsu, T.Nogi, N.Matsugaki, N.Igarashi, M.Suzuki, R.Kato, K.Nakayama, and S.Wakatsuki (2003).
Molecular mechanism of membrane recruitment of GGA by ARF in lysosomal protein transport.
  Nat Struct Biol, 10, 386-393.
PDB codes: 1j2h 1j2i 1j2j 1o3x 1o3y
12429613 S.Pasqualato, L.Renault, and J.Cherfils (2002).
Arf, Arl, Arp and Sar proteins: a family of GTP-binding proteins with a structural device for 'front-back' communication.
  EMBO Rep, 3, 1035-1041.  
12239560 X.Bi, R.A.Corpina, and J.Goldberg (2002).
Structure of the Sec23/24-Sar1 pre-budding complex of the COPII vesicle coat.
  Nature, 419, 271-277.
PDB codes: 1m2o 1m2v
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