PDBsum entry 1mfl

Go to PDB code: 
protein ligands links
Signaling protein PDB id
Protein chain
95 a.a. *
Waters ×72
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: The structure of erbin pdz domain bound to the carboxy- terminal tail of the erbb2 receptor
Structure: Erb-b2 interacting protein. Chain: a. Fragment: pdz domain. Engineered: yes. Phosphorylated erb-b2 carboxyl-terminal fragment.. Chain: b. Fragment: peptide ldvpv. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: peptide synthesized chemically
Biol. unit: Dimer (from PQS)
1.88Å     R-factor:   0.169     R-free:   0.216
Authors: G.Birrane,J.Chung,J.A.Ladias
Key ref:
G.Birrane et al. (2003). Novel mode of ligand recognition by the Erbin PDZ domain. J Biol Chem, 278, 1399-1402. PubMed id: 12444095 DOI: 10.1074/jbc.C200571200
12-Aug-02     Release date:   21-Jan-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q96RT1  (LAP2_HUMAN) -  Protein LAP2
1412 a.a.
95 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)


DOI no: 10.1074/jbc.C200571200 J Biol Chem 278:1399-1402 (2003)
PubMed id: 12444095  
Novel mode of ligand recognition by the Erbin PDZ domain.
G.Birrane, J.Chung, J.A.Ladias.
Erbin contains a class I PDZ domain that binds to the C-terminal region of the receptor tyrosine kinase ErbB2, a class II ligand. The crystal structure of the human Erbin PDZ bound to the peptide EYLGLDVPV corresponding to the C-terminal residues 1247-1255 of human ErbB2 has been determined at 1.25-A resolution. The Erbin PDZ deviates from the canonical PDZ fold in that it contains a single alpha-helix. The isopropyl group of valine at position -2 of the ErbB2 peptide interacts with the Erbin Val(1351) and displaces the peptide backbone away from the alpha-helix, elucidating the molecular basis of class II ligand recognition by a class I PDZ domain. Strikingly, the phenolic ring of tyrosine -7 enters into a pocket formed by the extended beta 2-beta 3 loop of the Erbin PDZ. Phosphorylation of tyrosine -7 abolishes this interaction but does not affect the binding of the four C-terminal peptidic residues to PDZ, as revealed by the crystal structure of the Erbin PDZ complexed with a phosphotyrosine-containing ErbB2 peptide. Since phosphorylation of tyrosine -7 plays a critical role in ErbB2 function, the selective binding and sequestration of this residue in its unphosphorylated state by the Erbin PDZ provides a novel mechanism for regulation of the ErbB2-mediated signaling and oncogenicity.
  Selected figure(s)  
Figure 1.
Fig. 1. Structure of the Erbin PDZ bound to the unphosphorylated ErbB2 peptide. A, sequence comparison of selected class I PDZ domains. Identical residues in four or more domains are shown as white letters on blue background. Hyphens represent gaps inserted for optimum alignment. The secondary structure of the Erbin PDZ is indicated at the top. Residues forming a short -helix in PDZs with known structures are enclosed in a red box. B, stereo view of the Erbin PDZ bound to the peptide EYLGLDVPV. The figure was made using BOBSCRIPT (30) and POV-Ray ( C, surface topology of the Erbin PDZ bound to the ErbB2 peptide. The figure was made using GRASP (31). D, two-dimensional representation of the interactions between Erbin PDZ residues (orange) and the peptide (purple). Water molecules (W) are shown as cyan spheres, hydrogen bonds as dashed lines, and hydrophobic interactions as arcs with radial spokes. The figure was made using LIGPLOT (32). E, stereo view of a weighted 2F[obs] F[calc] electron density map at the P[2] pocket calculated at 1.25 Å and contoured at 2.5 .
Figure 2.
Fig. 2. Structure of the Erbin PDZ bound to the phosphorylated ErbB2 peptide. A, stereo view of the Erbin PDZ bound to the peptide EpYLGLDVPV. A weighted 2F[obs] F[calc] electron density map calculated at 1.88-Å resolution and contoured at 1.0 is superimposed on the ErbB2 peptide. B, superposition of the C backbone traces of Erbin PDZ-peptide (pink), Erbin PDZ-phosphopeptide (blue), and PSD-95 PDZ3-peptide (yellow) (Protein Data Bank code 1BE9). Side chains of the peptidic residues, Erbin His1347 and Val1351, and PSD-95 His372 are shown as stick models.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 1399-1402) copyright 2003.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21283644 A.J.Te Velthuis, P.A.Sakalis, D.A.Fowler, and C.P.Bagowski (2011).
Genome-Wide Analysis of PDZ Domain Binding Reveals Inherent Functional Overlap within the PDZ Interaction Network.
  PLoS One, 6, e16047.  
21422294 B.Balana, I.Maslennikov, W.Kwiatkowski, K.M.Stern, L.Bahima, S.Choe, and P.A.Slesinger (2011).
Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27.
  Proc Natl Acad Sci U S A, 108, 5831-5836.
PDB codes: 3qdo 3qe1 3qgl
21376703 J.H.Lee, H.Park, S.J.Park, H.J.Kim, and S.H.Eom (2011).
The structural flexibility of the shank1 PDZ domain is important for its binding to different ligands.
  Biochem Biophys Res Commun, 407, 207-212.
PDB codes: 3qjm 3qjn
20586101 M.Popovic, J.Bella, V.Zlatev, V.Hodnik, G.Anderluh, P.N.Barlow, A.Pintar, and S.Pongor (2011).
The interaction of Jagged-1 cytoplasmic tail with afadin PDZ domain is local, folding-independent, and tuned by phosphorylation.
  J Mol Recognit, 24, 245-253.  
20608975 C.Roghi, L.Jones, M.Gratian, W.R.English, and G.Murphy (2010).
Golgi reassembly stacking protein 55 interacts with membrane-type (MT) 1-matrix metalloprotease (MMP) and furin and plays a role in the activation of the MT1-MMP zymogen.
  FEBS J, 277, 3158-3175.  
20047332 R.C.Tyler, F.C.Peterson, and B.F.Volkman (2010).
Distal interactions within the par3-VE-cadherin complex.
  Biochemistry, 49, 951-957.
PDB code: 2koh
20016085 A.Swistowski, Q.Zhang, M.E.Orcholski, D.Crippen, C.Vitelli, A.Kurakin, and D.E.Bredesen (2009).
Novel mediators of amyloid precursor protein signaling.
  J Neurosci, 29, 15703-15712.  
19228696 B.Sulka, H.Lortat-Jacob, R.Terreux, F.Letourneur, and P.Rousselle (2009).
Tyrosine dephosphorylation of the syndecan-1 PDZ binding domain regulates syntenin-1 recruitment.
  J Biol Chem, 284, 10659-10671.  
19828436 C.M.Petit, J.Zhang, P.J.Sapienza, E.J.Fuentes, and A.L.Lee (2009).
Hidden dynamic allostery in a PDZ domain.
  Proc Natl Acad Sci U S A, 106, 18249-18254.  
19624188 I.Meliciani, K.Klenin, T.Strunk, K.Schmitz, and W.Wenzel (2009).
Probing hot spots on protein-protein interfaces with all-atom free-energy simulation.
  J Chem Phys, 131, 034114.  
19685007 M.A.Durney, G.Birrane, C.Anklin, A.Soni, and J.A.Ladias (2009).
Solution structure of the human Tax-interacting protein-1.
  J Biomol NMR, 45, 329-334.
PDB code: 2kg2
19569188 T.Beuming, R.Farid, and W.Sherman (2009).
High-energy water sites determine peptide binding affinity and specificity of PDZ domains.
  Protein Sci, 18, 1609-1619.  
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.  
18523588 A.Di Segni, K.Farin, and R.Pinkas-Kramarski (2008).
Identification of nucleolin as new ErbB receptors- interacting protein.
  PLoS ONE, 3, e2310.  
18411422 J.Liu, J.Zhang, Y.Yang, H.Huang, W.Shen, Q.Hu, X.Wang, J.Wu, and Y.Shi (2008).
Conformational change upon ligand binding and dynamics of the PDZ domain from leukemia-associated Rho guanine nucleotide exchange factor.
  Protein Sci, 17, 1003-1014.  
17895993 A.Kurakin, A.Swistowski, S.C.Wu, and D.E.Bredesen (2007).
The PDZ domain as a complex adaptive system.
  PLoS ONE, 2, e953.  
17474715 D.Saro, T.Li, C.Rupasinghe, A.Paredes, N.Caspers, and M.R.Spaller (2007).
A thermodynamic ligand binding study of the third PDZ domain (PDZ3) from the mammalian neuronal protein PSD-95.
  Biochemistry, 46, 6340-6352.  
17641200 M.A.Stiffler, J.R.Chen, V.P.Grantcharova, Y.Lei, D.Fuchs, J.E.Allen, L.A.Zaslavskaia, and G.MacBeath (2007).
PDZ domain binding selectivity is optimized across the mouse proteome.
  Science, 317, 364-369.  
17973281 P.Boisguerin, B.Ay, G.Radziwill, R.D.Fritz, K.Moelling, and R.Volkmer (2007).
Characterization of a putative phosphorylation switch: adaptation of SPOT synthesis to analyze PDZ domain regulation mechanisms.
  Chembiochem, 8, 2302-2307.  
17473018 Q.Chen, X.Niu, Y.Xu, J.Wu, and Y.Shi (2007).
Solution structure and backbone dynamics of the AF-6 PDZ domain/Bcr peptide complex.
  Protein Sci, 16, 1053-1062.
PDB code: 2ain
16671149 M.Joshi, C.Vargas, P.Boisguerin, A.Diehl, G.Krause, P.Schmieder, K.Moelling, V.Hagen, M.Schade, and H.Oschkinat (2006).
Discovery of low-molecular-weight ligands for the AF6 PDZ domain.
  Angew Chem Int Ed Engl, 45, 3790-3795.
PDB codes: 1xz9 2exg
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.  
16132821 A.E.Duquesne, M.Ruijter, J.Brouwer, J.W.Drijfhout, S.B.Nabuurs, C.A.Spronk, G.W.Vuister, M.Ubbink, and G.W.Canters (2005).
Solution structure of the second PDZ domain of the neuronal adaptor X11alpha and its interaction with the C-terminal peptide of the human copper chaperone for superoxide dismutase.
  J Biomol NMR, 32, 209-218.
PDB code: 1y7n
16207817 C.Haslekås, K.Breen, K.W.Pedersen, L.E.Johannessen, E.Stang, and I.H.Madshus (2005).
The inhibitory effect of ErbB2 on epidermal growth factor-induced formation of clathrin-coated pits correlates with retention of epidermal growth factor receptor-ErbB2 oligomeric complexes at the plasma membrane.
  Mol Biol Cell, 16, 5832-5842.  
16283141 E.Kalay, Brouwer, R.Caylan, S.B.Nabuurs, B.Wollnik, A.Karaguzel, J.G.Heister, H.Erdol, F.P.Cremers, C.W.Cremers, H.G.Brunner, and H.Kremer (2005).
A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.
  J Mol Med, 83, 1025-1032.  
16007100 J.F.Long, W.Feng, R.Wang, L.N.Chan, F.C.Ip, J.Xia, N.Y.Ip, and M.Zhang (2005).
Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem.
  Nat Struct Mol Biol, 12, 722-728.
PDB codes: 1u37 1u38 1u39 1u3b
15978037 L.C.van den Berk, E.Landi, E.Harmsen, L.Dente, and W.J.Hendriks (2005).
Redox-regulated affinity of the third PDZ domain in the phosphotyrosine phosphatase PTP-BL for cysteine-containing target peptides.
  FEBS J, 272, 3306-3316.  
14725761 T.Walma, J.Aelen, S.B.Nabuurs, M.Oostendorp, L.van den Berk, W.Hendriks, and G.W.Vuister (2004).
A closed binding pocket and global destabilization modify the binding properties of an alternatively spliced form of the second PDZ domain of PTP-BL.
  Structure, 12, 11-20.
PDB code: 1ozi
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
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.