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PDBsum entry 1uus

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protein links
Signal transduction PDB id
1uus
Jmol
Contents
Protein chain
465 a.a. *
Waters ×56
* Residue conservation analysis
PDB id:
1uus
Name: Signal transduction
Title: Structure of an activated dictyostelium stat in its DNA-unbound form
Structure: Stat protein. Chain: a. Fragment: residues 235-707. Engineered: yes
Source: Dictyostelium discoideum. Slime mold. Organism_taxid: 44689. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.8Å     R-factor:   0.198     R-free:   0.257
Authors: M.Soler-Lopez,C.Petosa,M.Fukuzawa,R.Ravelli,J.G.Williams, C.W.Muller
Key ref:
M.Soler-Lopez et al. (2004). Structure of an activated Dictyostelium STAT in its DNA-unbound form. Mol Cell, 13, 791-804. PubMed id: 15053873 DOI: 10.1016/S1097-2765(04)00130-3
Date:
09-Jan-04     Release date:   26-Mar-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O00910  (STATA_DICDI) -  Signal transducer and activator of transcription A
Seq:
Struc:
 
Seq:
Struc:
707 a.a.
465 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     signal transduction   2 terms 
  Biochemical function     signal transducer activity     3 terms  

 

 
DOI no: 10.1016/S1097-2765(04)00130-3 Mol Cell 13:791-804 (2004)
PubMed id: 15053873  
 
 
Structure of an activated Dictyostelium STAT in its DNA-unbound form.
M.Soler-Lopez, C.Petosa, M.Fukuzawa, R.Ravelli, J.G.Williams, C.W.Müller.
 
  ABSTRACT  
 
Dd-STATa is a STAT protein which transcriptionally regulates cellular differentiation in Dictyostelium discoideum, the only non-metazoan known to employ SH2 domain signaling. The 2.7 A crystal structure of a tyrosine phosphorylated Dd-STATa homodimer reveals a four-domain architecture similar to that of mammalian STATs 1 and 3, but with an inverted orientation for the coiled-coil domain. Dimerization is mediated by SH2 domain:phosphopeptide interactions and by a direct interaction between SH2 domains. The unliganded Dd-STATa dimer adopts a fully extended conformation remarkably different from that of the DNA-bound mammalian STATs, implying a large conformational change upon target site recognition. Buried hydrophilic residues predicted to destabilize the coiled-coil domain suggest how hydrophobic residues may become exposed and mediate nuclear export. Functional and evolutionary implications for metazoan STAT proteins are discussed.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Structure of the Dimer(A) Side view. The lower monomers of Dd-STATa and STAT3 are viewed as in Figure 2A. Asterisks mark the position of the Asn residue in segment 4 critical for DNA recognition.(B) View along the dyad axis. The STAT3 Ig and EF-hand domains are shown in transparent form. Arrows indicate the chain direction in tail segments.
Figure 4.
Figure 4. SH2 Domain and Dimer Interface(A) Comparison of the Dd-STATa (yellow) and STAT3 (green) SH2 domains. The Dd-STATa tail segment is in magenta; that of STAT3 is transparent. The Dd-STATa SH2 domain shares similar sequence identity with the mammalian STATs (18%–22%) as with Src (22%), but a common core of 65 residues is structurally more similar to Src (rmsd[Cα] = 1.13 Å) than to STAT1 (1.27Å) or STAT3 (1.47 Å).(B) Overview of the dimer interface. The view is roughly along the dyad but flipped relative to Figure 3B. The molecular surface and regions of negative (red) and positive (blue) potential are shown for monomer 2. The phosphotyrosine phosphate interacts with three Arg residues (lower right) and is highly buried (upper left). Arg693 is hydrogen bonded to Glu703 and to the backbone carbonyl of Ala695. This figure and Figure 5D were made with GRASP (Nicholls et al., 1991).(C) SH2-P interactions. The view is roughly that of monomer 1 in (B). Hydrogen bonds (dashed lines) are shown in black if common to class I SH2 domains, and in red otherwise. Interactions common to class I domains include phosphotyrosine recognition by Arg594, Arg612, and Ser614; a hydrogen bond between the backbone atoms of His636 (data not shown) and Glu703; and one between Arg594 and the backbone carbonyl of Gly701. Also common is the hydrophobic binding pocket for Leu705 (pY+3), which in Dd-STATa is formed by residues Tyr637, Phe654, His658, and Phe661. Interactions unique to Dd-STATa include those involving Arg616 (see text), a hydrogen bond from Lys635 to the carbonyl of Leu705, a salt bridge between Arg633 and Glu703, and a van der Waals contact between Gln660 and Asn706. For clarity, the side chain of Ser707 is omitted.(D) SH2-SH2 interactions viewed along the dyad axis. Side chains mediating SH2-SH2 contacts are in green (monomer 1) or yellow (monomer 2). Also shown are BG loop residues His658 and Phe661 (in gray) which interact with Leu705, and the hydrogen bond between the backbone of Glu657 and Asn706. For clarity, the side chain of Asn706 is in transparent form, and those of residues 629–630 are omitted.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2004, 13, 791-804) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21534947 T.Kawata (2011).
STAT signaling in Dictyostelium development.
  Dev Growth Differ, 53, 548-557.  
20660652 J.G.Williams (2010).
Dictyostelium finds new roles to model.
  Genetics, 185, 717-726.  
  19309697 P.Bernadó, Y.Pérez, J.Blobel, J.Fernández-Recio, D.I.Svergun, and M.Pons (2009).
Structural characterization of unphosphorylated STAT5a oligomerization equilibrium in solution by small-angle X-ray scattering.
  Protein Sci, 18, 716-726.  
18621723 B.J.Mayer (2008).
Clues to the evolution of complex signaling machinery.
  Proc Natl Acad Sci U S A, 105, 9453-9454.  
18058821 J.S.McMurray (2008).
Structural basis for the binding of high affinity phosphopeptides to Stat3.
  Biopolymers, 90, 69-79.  
18591661 N.Wenta, H.Strauss, S.Meyer, and U.Vinkemeier (2008).
Tyrosine phosphorylation regulates the partitioning of STAT1 between different dimer conformations.
  Proc Natl Acad Sci U S A, 105, 9238-9243.  
18192189 R.R.Copley (2008).
The animal in the genome: comparative genomics and evolution.
  Philos Trans R Soc Lond B Biol Sci, 363, 1453-1461.  
17435008 N.Shimada, and T.Kawata (2007).
Evidence that noncoding RNA dutA is a multicopy suppressor of Dictyostelium discoideum STAT protein Dd-STATa.
  Eukaryot Cell, 6, 1030-1040.  
18034310 Q.Zhu, and N.Jing (2007).
Computational study on mechanism of G-quartet oligonucleotide T40214 selectively targeting Stat3.
  J Comput Aided Mol Des, 21, 641-648.  
17182865 C.Mertens, M.Zhong, R.Krishnaraj, W.Zou, X.Chen, and J.E.Darnell (2006).
Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N-terminal domain.
  Genes Dev, 20, 3372-3381.  
17216035 C.P.Lim, and X.Cao (2006).
Structure, function, and regulation of STAT proteins.
  Mol Biosyst, 2, 536-550.  
15875012 L.Eichinger, J.A.Pachebat, G.Glöckner, M.A.Rajandream, R.Sucgang, M.Berriman, J.Song, R.Olsen, K.Szafranski, Q.Xu, B.Tunggal, S.Kummerfeld, M.Madera, B.A.Konfortov, F.Rivero, A.T.Bankier, R.Lehmann, N.Hamlin, R.Davies, P.Gaudet, P.Fey, K.Pilcher, G.Chen, D.Saunders, E.Sodergren, P.Davis, A.Kerhornou, X.Nie, N.Hall, C.Anjard, L.Hemphill, N.Bason, P.Farbrother, B.Desany, E.Just, T.Morio, R.Rost, C.Churcher, J.Cooper, S.Haydock, N.van Driessche, A.Cronin, I.Goodhead, D.Muzny, T.Mourier, A.Pain, M.Lu, D.Harper, R.Lindsay, H.Hauser, K.James, M.Quiles, M.Madan Babu, T.Saito, C.Buchrieser, A.Wardroper, M.Felder, M.Thangavelu, D.Johnson, A.Knights, H.Loulseged, K.Mungall, K.Oliver, C.Price, M.A.Quail, H.Urushihara, J.Hernandez, E.Rabbinowitsch, D.Steffen, M.Sanders, J.Ma, Y.Kohara, S.Sharp, M.Simmonds, S.Spiegler, A.Tivey, S.Sugano, B.White, D.Walker, J.Woodward, T.Winckler, Y.Tanaka, G.Shaulsky, M.Schleicher, G.Weinstock, A.Rosenthal, E.C.Cox, R.L.Chisholm, R.Gibbs, W.F.Loomis, M.Platzer, R.R.Kay, J.Williams, P.H.Dear, A.A.Noegel, B.Barrell, and A.Kuspa (2005).
The genome of the social amoeba Dictyostelium discoideum.
  Nature, 435, 43-57.  
15753310 M.Zhong, M.A.Henriksen, K.Takeuchi, O.Schaefer, B.Liu, J.ten Hoeve, Z.Ren, X.Mao, X.Chen, K.Shuai, and J.E.Darnell (2005).
Implications of an antiparallel dimeric structure of nonphosphorylated STAT1 for the activation-inactivation cycle.
  Proc Natl Acad Sci U S A, 102, 3966-3971.  
15937186 V.Oganesyan, N.Oganesyan, P.D.Adams, J.Jancarik, H.A.Yokota, R.Kim, and S.H.Kim (2005).
Crystal structure of the "PhoU-like" phosphate uptake regulator from Aquifex aeolicus.
  J Bacteriol, 187, 4238-4244.
PDB codes: 1t72 1t8b
  16511123 X.Mao, and X.Chen (2005).
Crystallization and X-ray crystallographic analysis of human STAT1.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 666-668.  
15780933 X.Mao, Z.Ren, G.N.Parker, H.Sondermann, M.A.Pastorello, W.Wang, J.S.McMurray, B.Demeler, J.E.Darnell, and X.Chen (2005).
Structural bases of unphosphorylated STAT1 association and receptor binding.
  Mol Cell, 17, 761-771.
PDB code: 1yvl
15380246 A.R.Kimmel, and R.A.Firtel (2004).
Breaking symmetries: regulation of Dictyostelium development through chemoattractant and morphogen signal-response.
  Curr Opin Genet Dev, 14, 540-549.  
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 codes are shown on the right.