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PDBsum entry 1tk7

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protein links
Signaling protein PDB id
1tk7
Jmol
Contents
Protein chain
88 a.a. *
* Residue conservation analysis
PDB id:
1tk7
Name: Signaling protein
Title: Nmr structure of ww domains (ww3-4) from suppressor of deltex
Structure: Cg4244-pb. Chain: a. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: su(dx). Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 7 models
Authors: O.Y.Fedoroff,J.M.Avis,A.P.Golovanov,M.Baron,S.A.Townson
Key ref:
O.Y.Fedoroff et al. (2004). The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex. J Biol Chem, 279, 34991-35000. PubMed id: 15173166 DOI: 10.1074/jbc.M404987200
Date:
08-Jun-04     Release date:   20-Jul-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9Y0H4  (SUDX_DROME) -  E3 ubiquitin-protein ligase Su(dx)
Seq:
Struc:
 
Seq:
Struc:
949 a.a.
88 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 

 
DOI no: 10.1074/jbc.M404987200 J Biol Chem 279:34991-35000 (2004)
PubMed id: 15173166  
 
 
The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.
O.Y.Fedoroff, S.A.Townson, A.P.Golovanov, M.Baron, J.M.Avis.
 
  ABSTRACT  
 
WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.
 
  Selected figure(s)  
 
Figure 4.
FIG. 4. A, structural alignment of the five lowest energy structures (of 20 generated) of the tandem WW3 and WW4 domains of Su(dx) in the liganded form. Superposition is based on the backbone of residues 12-41 (left)or37-85 (right). Only backbone atoms are shown, and residues 1-10 from the unstructured N terminus are omitted. WW3 residues are colored yellow, WW4 residues are colored blue, and the interdomain linker is colored red. Five structures only are shown for reasons of clarity. B, one of the structures shown in two orientations with secondary elements ( -strands) of WW domains shown as yellow arrows. The WW3 backbone is colored blue, WW4 backbone is colored white, and the linker is colored magenta. Side chains of Trp39 and Phe^83 are also shown.
Figure 6.
FIG. 6. Residual dipolar coupling measurements for liganded WW3-4. 1HN-15N RDC values are plotted versus residue number. -Strands of WW domains are shown by colored bars: green for the N-terminal WW domain (WW3) and blue for the C-terminal domain (WW4). The linker region is highlighted in yellow.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 34991-35000) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21200027 A.Djiane, H.Shimizu, M.Wilkin, S.Mazleyrat, M.D.Jennings, J.Avis, S.Bray, and M.Baron (2011).
Su(dx) E3 ubiquitin ligase-dependent and -independent functions of Polychaetoid, the Drosophila ZO-1 homologue.
  J Cell Biol, 192, 189-200.  
19557014 B.Yang, and S.Kumar (2010).
Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions.
  Cell Death Differ, 17, 68-77.  
20937913 P.A.Chong, H.Lin, J.L.Wrana, and J.D.Forman-Kay (2010).
Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity.
  Proc Natl Acad Sci U S A, 107, 18404-18409.
PDB code: 2kxq
19592703 X.Huang, M.Beullens, J.Zhang, Y.Zhou, E.Nicolaescu, B.Lesage, Q.Hu, J.Wu, M.Bollen, and Y.Shi (2009).
Structure and function of the two tandem WW domains of the pre-mRNA splicing factor FBP21 (formin-binding protein 21).
  J Biol Chem, 284, 25375-25387.
PDB code: 2jxw
18266980 A.M.Buga, M.Sascau, C.Pisoschi, J.G.Herndon, C.Kessler, and A.Popa-Wagner (2008).
The genomic response of the ipsilateral and contralateral cortex to stroke in aged rats.
  J Cell Mol Med, 12, 2731-2753.  
18604872 N.S.Nguyen Huu, W.D.Ryder, N.Zeps, M.Flasza, M.Chiu, A.M.Hanby, R.Poulsom, R.B.Clarke, and M.Baron (2008).
Tumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator.
  J Pathol, 216, 93.  
18799787 W.R.Gordon, K.L.Arnett, and S.C.Blacklow (2008).
The molecular logic of Notch signaling--a structural and biochemical perspective.
  J Cell Sci, 121, 3109-3119.  
  17284314 B.K.Ang, C.Y.Lim, S.S.Koh, N.Sivakumar, S.Taib, K.B.Lim, S.Ahmed, G.Rajagopal, and S.H.Ong (2007).
ArhGAP9, a novel MAP kinase docking protein, inhibits Erk and p38 activation through WW domain binding.
  J Mol Signal, 2, 1.  
17932789 O.Gileadi, S.Knapp, W.H.Lee, B.D.Marsden, S.Müller, F.H.Niesen, K.L.Kavanagh, L.J.Ball, F.von Delft, D.A.Doyle, U.C.Oppermann, and M.Sundström (2007).
The scientific impact of the Structural Genomics Consortium: a protein family and ligand-centered approach to medically-relevant human proteins.
  J Struct Funct Genomics, 8, 107-119.  
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.