PDBsum entry 1k9r

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Structural protein PDB id
Protein chain
40 a.a. *
* Residue conservation analysis
PDB id:
Name: Structural protein
Title: Yap65 ww domain complexed to acetyl-plppy
Structure: 65 kda yes-associated protein. Chain: a. Fragment: wild type ww domain. Synonym: yap65. Engineered: yes. Ww domain binding protein-1. Chain: b. Fragment: residues 149-153. Synonym: wbp-1.
Source: Synthetic: yes. Other_details: this sequence was synthetically obtained, by semiautomated spot synthesis in a cellulose support.. Other_details: this sequence was synthetically obtained by spot synthesis in a cellulose support.
NMR struc: 20 models
Authors: J.R.Pires,F.Taha-Nejad,F.Toepert,T.Ast,U.Hoffmuller, J.Schneider-Mergener,R.Kuhne,M.J.Macias,H.Oschkinat
Key ref:
J.R.Pires et al. (2001). Solution structures of the YAP65 WW domain and the variant L30 K in complex with the peptides GTPPPPYTVG, N-(n-octyl)-GPPPY and PLPPY and the application of peptide libraries reveal a minimal binding epitope. J Mol Biol, 314, 1147-1156. PubMed id: 11743730 DOI: 10.1006/jmbi.2000.5199
30-Oct-01     Release date:   28-Dec-01    
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Protein chain
Pfam   ArchSchema ?
P46937  (YAP1_HUMAN) -  Transcriptional coactivator YAP1
504 a.a.
40 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1006/jmbi.2000.5199 J Mol Biol 314:1147-1156 (2001)
PubMed id: 11743730  
Solution structures of the YAP65 WW domain and the variant L30 K in complex with the peptides GTPPPPYTVG, N-(n-octyl)-GPPPY and PLPPY and the application of peptide libraries reveal a minimal binding epitope.
J.R.Pires, F.Taha-Nejad, F.Toepert, T.Ast, U.Hoffmüller, J.Schneider-Mergener, R.Kühne, M.J.Macias, H.Oschkinat.
The single mutation L30 K in the Hu-Yap65 WW domain increased the stability of the complex with the peptide GTPPPPYTVG (K(d)=40(+/-5) microM). Here we report the refined solution structure of this complex by NMR spectroscopy and further derived structure-activity relationships by using ligand peptide libraries with truncated sequences and a substitution analysis that yielded acetyl-PPPPY as the smallest high-affinity binding peptide (K(d)=60 microM). The structures of two new complexes with weaker binding ligands chosen based on these results (N-(n-octyl)-GPPPYNH(2) and Ac-PLPPY) comprising the wild-type WW domain of Hu-Yap65 were determined. Comparison of the structures of the three complexes were useful for identifying the molecular basis of high-affinity: hydrophobic and specific interactions between the side-chains of Y28 and W39 and P5' and P4', respectively, and hydrogen bonds between T37 (donnor) and P5' (acceptor) and between W39 (donnor) and T2' (acceptor) stabilize the complex.The structure of the complex L30 K Hu-Yap65 WW domain/GTPPPPYTVG is compared to the published crystal structure of the dystrophin WW domain bound to a segment of the beta-dystroglycan protein and to the solution structure of the first Nedd4 WW domain and its prolin-rich ligand, suggesting that WW sequences bind proline-rich peptides in an evolutionary conserved fashion. The position equivalent to T22 in the Hu-Yap65 WW domain sequence is seen as responsible for differentiation in the binding mode among the WW domains of group I.
  Selected figure(s)  
Figure 4.
Figure 4. (a) Cartoon representation of the structure of the the complex L30K Hu-Yap WW domain/GTPPPPYTVG. (b) Poly-proline peptide bound to the surface of the L30K Hu-Yap65 WW domain; the surface is coloured by lipophilicity, in brown the more lipophilic regions and in green more hydrophilic. Hydrogen bond donnors are coloured red.
Figure 5.
Figure 5. Comparison of the structures. (a) Superposition of the structures of the complexes of the Hu-Yap65 WW domain: L30 K WW domain and the peptide GTPPPPYTVG (black), wild-type WW domain and the petide N-(n-octyl)-GPPPY-NH[2] (green) and wild-type WW domain and the peptide acetyl-PLPPY (magenta). (b) L30K WW domain of the Hu-Yap65 and the peptide GTPPPPYTVG (complex 1, black) superimposed to the complex formed by the WW domain of dystrophin and a poly-proline containing fragment of dystroglican (blue). (c) L30K WW domain of the Hu-Yap65 and the peptide GTPPPPYTVG (complex 1, black) superimposed to the complex formed by the WW domain of Nedd4 and its proline-rich ligand (red). The structures were superimposed by the a-carbon atoms of the residues that compose the binding pocket (T22, Y28, L30 or K30, H32, Q35, T37 and W39) and are the only residues displayed together with the ligands.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 314, 1147-1156) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20711194 D.M.Fowler, C.L.Araya, S.J.Fleishman, E.H.Kellogg, J.J.Stephany, D.Baker, and S.Fields (2010).
High-resolution mapping of protein sequence-function relationships.
  Nat Methods, 7, 741-746.  
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
18941632 M.Cardó-Vila, A.J.Zurita, R.J.Giordano, J.Sun, R.Rangel, L.Guzman-Rojas, C.D.Anobom, A.P.Valente, F.C.Almeida, J.Lahdenranta, M.G.Kolonin, W.Arap, and R.Pasqualini (2008).
A ligand peptide motif selected from a cancer patient is a receptor-interacting site within human interleukin-11.
  PLoS ONE, 3, e3452.  
17437719 B.Morales, X.Ramirez-Espain, A.Z.Shaw, P.Martin-Malpartida, F.Yraola, E.Sánchez-Tilló, C.Farrera, A.Celada, M.Royo, and M.J.Macias (2007).
NMR structural studies of the ItchWW3 domain reveal that phosphorylation at T30 inhibits the interaction with PPxY-containing ligands.
  Structure, 15, 473-483.
PDB codes: 2jo9 2joc
17502622 J.D.Kulman, J.E.Harris, L.Xie, and E.W.Davie (2007).
Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein that binds to the transcriptional coactivator Yes-associated protein.
  Proc Natl Acad Sci U S A, 104, 8767-8772.  
17656366 M.D.Jennings, R.T.Blankley, M.Baron, A.P.Golovanov, and J.M.Avis (2007).
Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex.
  J Biol Chem, 282, 29032-29042.
PDB code: 2jmf
17586778 M.Jäger, H.Nguyen, M.Dendle, M.Gruebele, and J.W.Kelly (2007).
Influence of hPin1 WW N-terminal domain boundaries on function, protein stability, and folding.
  Protein Sci, 16, 1495-1501.  
17766370 T.Sharpe, A.L.Jonsson, T.J.Rutherford, V.Daggett, and A.R.Fersht (2007).
The role of the turn in beta-hairpin formation during WW domain folding.
  Protein Sci, 16, 2233-2239.  
16518883 J.Chocholousová, and M.Feig (2006).
Balancing an accurate representation of the molecular surface in generalized born formalisms with integrator stability in molecular dynamics simulations.
  J Comput Chem, 27, 719-729.  
16575938 J.Przezdziak, S.Tremmel, I.Kretzschmar, M.Beyermann, M.Bienert, and R.Volkmer-Engert (2006).
Probing the ligand-binding specificity and analyzing the folding state of SPOT-synthesized FBP28 WW domain variants.
  Chembiochem, 7, 780-788.  
16606443 J.R.Hesselberth, J.P.Miller, A.Golob, J.E.Stajich, G.A.Michaud, and S.Fields (2006).
Comparative analysis of Saccharomyces cerevisiae WW domains and their interacting proteins.
  Genome Biol, 7, R30.  
16641086 P.A.Chong, H.Lin, J.L.Wrana, and J.D.Forman-Kay (2006).
An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2.
  J Biol Chem, 281, 17069-17075.
PDB code: 2djy
16531238 V.Kanelis, M.C.Bruce, N.R.Skrynnikov, D.Rotin, and J.D.Forman-Kay (2006).
Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex.
  Structure, 14, 543-553.
PDB code: 2ez5
15800888 J.F.Espinosa, F.A.Syud, and S.H.Gellman (2005).
An autonomously folding beta-hairpin derived from the human YAP65 WW domain: attempts to define a minimum ligand-binding motif.
  Biopolymers, 80, 303-311.  
15880548 L.J.Ball, R.Kühne, J.Schneider-Mergener, and H.Oschkinat (2005).
Recognition of Proline-Rich Motifs by Protein-Protein-Interaction Domains.
  Angew Chem Int Ed Engl, 44, 2852-2869.  
15657931 M.V.Cubellis, F.Caillez, T.L.Blundell, and S.C.Lovell (2005).
Properties of polyproline II, a secondary structure element implicated in protein-protein interactions.
  Proteins, 58, 880-892.  
15558745 P.J.Winn, J.N.Battey, K.Schleinkofer, A.Banerjee, and R.C.Wade (2005).
Issues in high-throughput comparative modelling: a case study using the ubiquitin E2 conjugating enzymes.
  Proteins, 58, 367-375.  
14981252 J.Karanicolas, and C.L.Brooks (2004).
Integrating folding kinetics and protein function: biphasic kinetics and dual binding specificity in a WW domain.
  Proc Natl Acad Sci U S A, 101, 3432-3437.  
15173166 O.Y.Fedoroff, S.A.Townson, A.P.Golovanov, M.Baron, and J.M.Avis (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.
PDB code: 1tk7
12592019 L.Otte, U.Wiedemann, B.Schlegel, J.R.Pires, M.Beyermann, P.Schmieder, G.Krause, R.Volkmer-Engert, J.Schneider-Mergener, and H.Oschkinat (2003).
WW domain sequence activity relationships identified using ligand recognition propensities of 42 WW domains.
  Protein Sci, 12, 491-500.  
12654927 P.C.Henry, V.Kanelis, M.C.O'Brien, B.Kim, I.Gautschi, J.Forman-Kay, L.Schild, and D.Rotin (2003).
Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channel.
  J Biol Chem, 278, 20019-20028.  
12209469 R.K.Salinas, C.S.Shida, T.A.Pertinhez, A.Spisni, C.R.Nakaie, A.C.Paiva, and S.Schreier (2002).
Trifluoroethanol and binding to model membranes stabilize a predicted turn in a peptide corresponding to the first extracellular loop of the angiotensin II AT(1A) receptor.
  Biopolymers, 65, 21-31.  
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.