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PDBsum entry 1i8h

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Membrane protein/isomerase PDB id
1i8h
Jmol
Contents
Protein chains
13 a.a.
39 a.a. *
* Residue conservation analysis

References listed in PDB file
Key reference
Title 1h nmr study on the binding of pin1 trp-Trp domain with phosphothreonine peptides.
Authors R.Wintjens, J.M.Wieruszeski, H.Drobecq, P.Rousselot-Pailley, L.Buée, G.Lippens, I.Landrieu.
Ref. J Biol Chem, 2001, 276, 25150-25156. [DOI no: 10.1074/jbc.M010327200]
PubMed id 11313338
Abstract
The recent crystal structure of Pin1 protein bound to a doubly phosphorylated peptide from the C-terminal domain of RNA polymerase II revealed that binding interactions between Pin1 and its substrate take place through its Trp-Trp (WW) domain at the level of the loop Ser(11)-Arg(12) and the aromatic pair Tyr(18)-Trp(29), and showed a trans conformation for both pSer-Pro peptide bonds. However, the orientation of the ligand in the aromatic recognition groove still could be sequence-specific, as previously observed in SH3 domains complexed by peptide ligands or for different class of WW domains (Zarrinpar, A., and Lim, W. A. (2000) Nat. Struct. Biol. 7, 611-613). Because the bound peptide conformation could also differ as observed for peptide ligands bound to the 14-3-3 domain, ligand orientation and conformation for two other biologically relevant monophosphate substrates, one derived from the Cdc25 phosphatase of Xenopus laevis (EQPLpTPVTDL) and another from the human tau protein (KVSVVRpTPPKSPS) in complex with the WW domain are here studied by solution NMR methods. First, the proton resonance perturbations on the WW domain upon complexation with both peptide ligands were determined to be essentially located in the positively charged beta-hairpin Ser(11)-Gly(15) and around the aromatic Trp(29). Dissociation equilibrium constants of 117 and 230 microm for Cdc25 and tau peptides, respectively, were found. Several intermolecular nuclear Overhauser effects between WW domain and substrates were obtained from a ligand-saturated solution and were used to determine the structures of the complexes in solution. We found a similar N to C orientation as the one observed in the crystal complex structure of Pin1 and a trans conformation for the pThr-Pro peptidic bond in both peptide ligands, thereby indicating a unique binding scheme for the Pin1 WW domain to its multiple substrates.
Figure 5.
Fig. 5. Stereo view of the overlaid backbone traces of the 20 final conformers of the complex between the Pin1 WW domain and a Cdc25 peptide ligand. Superposition was done on residues (4-32) of the WW domain.
Figure 6.
Fig. 6. Ribbon drawing of the NMR reference structure of the complex between Pin1 WW domain (in light blue) and phosphopeptide ligand (in red), in comparison with the orientation of the CTD peptide (in violet) from the crystallographic model of the complex (13). The image was obtained by backbone superimposition of WW domains from our NMR complex and from the CTD peptide/Pin1 complex (13). Only the WW domain from this study and both phosphopeptide ligands are represented. Side chains implicated into the binding interface are labeled (in white for the WW domain residues and yellow for the ligand residues) and depicted in detail, as well as the amino acid pair Trp6-Pro32 of the WW domain. N atoms are blue and P atoms are violet. C atoms are green in the WW domain and orange in the tau ligand.
The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 25150-25156) copyright 2001.
PROCHECK
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