PDBsum entry 2ain

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Cell adhesion/transferase PDB id
Protein chain
93 a.a. *
* Residue conservation analysis
PDB id:
Name: Cell adhesion/transferase
Title: Solution structure of the af-6 pdz domain complexed with thE C-terminal peptide from the bcr protein
Structure: Afadin. Chain: a. Fragment: af-6 pdz domain. Synonym: af-6 protein. Engineered: yes. 6-mer peptide from breakpoint cluster region protein. Chain: b. Fragment: c-terminal peptide.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in humans.
NMR struc: 20 models
Authors: Q.Chen,J.Wu,Y.Shi
Key ref:
Q.Chen et al. (2007). Solution structure and backbone dynamics of the AF-6 PDZ domain/Bcr peptide complex. Protein Sci, 16, 1053-1062. PubMed id: 17473018 DOI: 10.1110/ps.062440607
30-Jul-05     Release date:   18-Jul-06    
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Protein chain
Pfam   ArchSchema ?
P55196  (AFAD_HUMAN) -  Afadin
1824 a.a.
93 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell-cell junction   1 term 


DOI no: 10.1110/ps.062440607 Protein Sci 16:1053-1062 (2007)
PubMed id: 17473018  
Solution structure and backbone dynamics of the AF-6 PDZ domain/Bcr peptide complex.
Q.Chen, X.Niu, Y.Xu, J.Wu, Y.Shi.
The human AF-6, a scaffold protein between cell membrane-associated proteins and the actin cytoskeleton, plays an important role in special cell-cell junctions and signal transduction. It can be phosphorylated by the protein kinase Bcr, which allows efficient binding of the C terminus of Bcr to the PDZ domain of AF-6 and consequently enhances the binding affinity of AF-6 to Ras. Formation of the AF-6, Bcr, and Ras ternary complex results in down-regulation of the Ras-mediated signal transduction pathway. To better understand the molecular basis for the recognition of the AF-6 PDZ domain and Bcr, we solve the solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide of Bcr and explore the interactions between them in detail. Compared with previously reported structures, the complex exhibits a noncanonical binding mode of PDZ/peptide. Owing to the distinct residues involved in the AF-6 PDZ domain and Bcr peptide interaction, the interaction mode does not adapt to the existing classification rules that have been put forward, based on the ligand or the PDZ domain specificity. Furthermore, the PDZ domain of AF-6 can bind to the C terminus of Bcr efficiently after phosphorylation of AF-6 by the Bcr kinase. The phosphorylation may induce a conformational change of AF-6, which makes the binding surface on the PDZ domain accessible to Bcr for efficient binding. This study not only characterizes the structural details of the AF-6 PDZ/Bcr peptide complex, but also provides a potential target for future drug design and disease therapy.
  Selected figure(s)  
Figure 1.
Structure of the AF-6 PDZ/Bcr complex. (A) Backbone overlay stereoview of the 20 lowest-energy NMR structures of the PDZ domain from human AF-6 complexed with the C-terminal peptide from Bcr, superimposed using backbone atoms (N, C[[alpha], C[prime prime or minute]). (Blue) The PDZ domain; (purple) the Bcr peptide. This figure was prepared using MOLMOL (Koradi et al. 1996). (B) Ribbon diagram of a representative NMR structure of the complex generated with MOLSCRIPT (Kraulis 1991) and Raster3D (Merritt and Murphy 1994). The [beta]-strands of the PDZ domain are labeled [beta]A --[beta]F, and the [alpha]-helices are labeled [alpha]A and [alpha]B. The ligand peptide ([beta]0) inserts between the [beta]B-strand and the [alpha]B-helix of the PDZ domain, forming an antiparallel [beta]-sheet with [beta]B.
Figure 2.
Detailed interaction between the AF-6 PDZ and Bcr peptide. (A) Structural comparison between (left) AF-6 PDZ/Bcr and (right) the canonical class I complex (PSD-95 PDZ3/peptide, PDB code 1BE9). Hydrogen bonds (dotted pink lines) between residues of the PDZ domain (blue) and the Bcr peptide (yellow) were deduced from the geometry of the structure. (Red) Oxygen atoms; (green) nitrogen atoms. The AF-6 PDZ/Bcr interaction differs significantly from that of the canonical class I PDZ domains for the absence of a hydrogen bond between the [minus sign]2 position residue of the peptide and the [alpha]B:1-position residue His of the PDZ. For clarity, side chains of only selected residues are shown. The programs MOLSCRIPT and Raster3D were used to generate this figure. (B) Structural comparison between (left) AF-6 PDZ/Bcr and (right) the canonical class II complex (Grip1 PDZ6/peptide, PDB code 1N7F). Surface representation of the packing interface is generated with PyMOL (available at (Yellow) The hydrophobic residues (Ala, Ile, Leu, Met, Pro, Phe, Tyr, and Val); (red) negatively charged residues (Asp and Glu); (blue) positively charged residues (Arg, His, and Lys); and (white) polar residues (Asn, Gln, Gly, Ser, and Thr). The AF-6 PDZ/Bcr interaction differs obviously from that of the canonical class II PDZ domains for the absence of the second hydrophobic pocket at the [minus sign]2 position residue of the ligand peptide.
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2007, 16, 1053-1062) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
17763922 Y.Shi, and J.Wu (2007).
Structural basis of protein-protein interaction studied by NMR.
  J Struct Funct Genomics, 8, 67-72.  
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