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PDBsum entry 1gq5

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protein metals links
Signaling protein PDB id
1gq5
Jmol
Contents
Protein chain
91 a.a. *
Metals
_CL ×2
Waters ×55
* Residue conservation analysis
PDB id:
1gq5
Name: Signaling protein
Title: Structural determinants of the nherf interaction with beta2-ar and pdgfr
Structure: Ezrin-radixin-moesin binding phosphoprotein-50. Chain: a. Fragment: pdz1 domain, residues 11-94. Synonym: na+/h+ exchanger regulatory factor. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
2.20Å     R-factor:   0.225     R-free:   0.263
Authors: S.Karthikeyan,T.Leung,J.A.A.Ladias
Key ref:
S.Karthikeyan et al. (2002). Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors. J Biol Chem, 277, 18973-18978. PubMed id: 11882663 DOI: 10.1074/jbc.M201507200
Date:
20-Nov-01     Release date:   14-Nov-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P09619  (PGFRB_HUMAN) -  Platelet-derived growth factor receptor beta
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1106 a.a.
91 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 75 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.1  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
ATP
+ [protein]-L-tyrosine
= ADP
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M201507200 J Biol Chem 277:18973-18978 (2002)
PubMed id: 11882663  
 
 
Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors.
S.Karthikeyan, T.Leung, J.A.Ladias.
 
  ABSTRACT  
 
The Na(+)/H(+) exchanger regulatory factor (NHERF) binds through its PDZ1 domain to the carboxyl-terminal sequences NDSLL and EDSFL of the beta(2) adrenergic receptor (beta(2)AR) and platelet-derived growth factor receptor, respectively, and plays a critical role in the membrane localization and physiological regulation of these receptors. The crystal structures of the human NHERF PDZ1 domain bound to the sequences NDSLL and EDSFL have been determined at 1.9- and 2.2-A resolution, respectively. The beta(2)AR and platelet-derived growth factor receptor ligands insert into the PDZ1 binding pocket by a beta-sheet augmentation process and are stabilized by largely similar networks of hydrogen bonds and hydrophobic contacts. In the PDZ1-beta(2)AR complex, the side chain of asparagine at position -4 in the beta(2)AR peptide forms two additional hydrogen bonds with Gly(30) of PDZ1, which contribute to the higher affinity of this interaction. Remarkably, both complexes are further stabilized by hydrophobic interactions involving the side chains of the penultimate amino acids of the peptide ligands, whereas the PDZ1 residues Asn(22) and Glu(43) undergo conformational changes to accommodate these side chains. These results provide structural insights into the mechanisms by which different side chains at the position -1 of peptide ligands interact with PDZ domains and contribute to the affinity of the PDZ-ligand interaction.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Structure of the hNHERF PDZ1 domain bound to the [2]AR and PDGFR carboxyl-terminal sequences. A, sequences of the chimeric hNHERF PDZ1- [2]AR (PDZ1B) and PDZ1-PDGFR (PDZ1P) proteins used in this study. Amino acid residues belonging to the [2]AR and PDGFR carboxyl termini are shaded in yellow. Secondary structure elements are indicated at the top. B, stereo view of the hNHERF PDZ1- [2]AR crystal packing. Each carboxyl terminus serves as a ligand for a neighboring PDZ1 molecule. C, ribbon diagram of the hNHERF PDZ1 domain bound to the [2]AR carboxyl-terminal sequence NDSLL. A weighted 2F[obs] F[calc] electron density map calculated at 1.9-Å resolution and contoured at 1.0 is superimposed on the [2]AR ligand. D, ribbon diagram of the hNHERF PDZ1 domain bound to the PDGFR carboxyl-terminal sequence EDSFL. A weighted 2F[obs] F[calc] electron density map calculated at 2.2-Å resolution and contoured at 1.0 is superimposed on the PDGFR ligand. The figure was made using MOLSCRIPT (35), BOBSCRIPT (36), Raster3D (37), and POV-Ray (www.povray.org).
Figure 2.
Fig. 2. PDZ1 interaction with the [2]AR and PDGFR carboxyl termini. A and B, stereo images of the hNHERF PDZ1 binding pocket bound to the [2]AR (A) and PDGFR (B) carboxyl-terminal ligands. Carbon, oxygen, and nitrogen atoms are shown in black, red, and blue, respectively. Water molecules are depicted as green spheres, and hydrogen bonds are shown as dashed lines. C and D, two-dimensional representations of the interactions observed between the hNHERF PDZ1 residues (orange) and [2]AR (C) or PDGFR (D) peptide ligands (purple). Dashed lines denote hydrogen bonds, and numbers indicate hydrogen bond lengths in Å. Hydrophobic interactions are shown as arcs with radial spokes. C and D were generated using LIGPLOT (38). E, superposition of the hNHERF PDZ1 bound to CFTR (yellow), [2]AR (blue), and PDGFR (pink) peptide ligands. For clarity, the 2 strand and 2 helix of the PDZ1 domain are shown as ribbon diagrams, and only the C^ traces are shown for the remaining PDZ1 main chain. Side chains of the peptide ligands and the PDZ1 residues Asn22 and Glu43 are shown as ball-and-stick models.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 18973-18978) copyright 2002.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19446522 H.Cheng, J.Li, R.Fazlieva, Z.Dai, Z.Bu, and H.Roder (2009).
Autoinhibitory interactions between the PDZ2 and C-terminal domains in the scaffolding protein NHERF1.
  Structure, 17, 660-669.
PDB code: 2jxo
19591839 J.Li, D.J.Callaway, and Z.Bu (2009).
Ezrin induces long-range interdomain allostery in the scaffolding protein NHERF1.
  J Mol Biol, 392, 166-180.  
19585657 Z.N.Gerek, O.Keskin, and S.B.Ozkan (2009).
Identification of specificity and promiscuity of PDZ domain interactions through their dynamic behavior.
  Proteins, 77, 796-811.  
17962403 S.T.Runyon, Y.Zhang, B.A.Appleton, S.L.Sazinsky, P.Wu, B.Pan, C.Wiesmann, N.J.Skelton, and S.S.Sidhu (2007).
Structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3.
  Protein Sci, 16, 2454-2471.
PDB codes: 2joa 2p3w
17656586 Y.Zhang, B.A.Appleton, P.Wu, C.Wiesmann, and S.S.Sidhu (2007).
Structural and functional analysis of the ligand specificity of the HtrA2/Omi PDZ domain.
  Protein Sci, 16, 1738-1750.
PDB code: 2pzd
17002371 N.Basdevant, H.Weinstein, and M.Ceruso (2006).
Thermodynamic basis for promiscuity and selectivity in protein-protein interactions: PDZ domains, a case study.
  J Am Chem Soc, 128, 12766-12777.  
15123239 P.Boisguerin, R.Leben, B.Ay, G.Radziwill, K.Moelling, L.Dong, and R.Volkmer-Engert (2004).
An improved method for the synthesis of cellulose membrane-bound peptides with free C termini is useful for PDZ domain binding studies.
  Chem Biol, 11, 449-459.  
12592016 A.C.Hamilton, J.Inglese, and M.Ferrer (2003).
A PDZ domain-based assay for measuring HIV protease activity: assay design considerations.
  Protein Sci, 12, 458-467.  
12842047 B.S.Kang, D.R.Cooper, Y.Devedjiev, U.Derewenda, and Z.S.Derewenda (2003).
Molecular roots of degenerate specificity in syntenin's PDZ2 domain: reassessment of the PDZ recognition paradigm.
  Structure, 11, 845-853.
PDB codes: 1nte 1obx 1oby 1obz
12547433 S.S.Sidhu, G.D.Bader, and C.Boone (2003).
Functional genomics of intracellular peptide recognition domains with combinatorial biology methods.
  Curr Opin Chem Biol, 7, 97.  
12512072 S.S.Sidhu, W.J.Fairbrother, and K.Deshayes (2003).
Exploring protein-protein interactions with phage display.
  Chembiochem, 4, 14-25.  
12881487 V.Raghuram, H.Hormuth, and J.K.Foskett (2003).
A kinase-regulated mechanism controls CFTR channel gating by disrupting bivalent PDZ domain interactions.
  Proc Natl Acad Sci U S A, 100, 9620-9625.  
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.