2AIN

Solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide from the Bcr protein


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Solution structure and backbone dynamics of the AF-6 PDZ domain/Bcr peptide complex.

Chen, Q.Niu, X.Xu, Y.Wu, J.Shi, Y.

(2007) Protein Sci 16: 1053-1062

  • DOI: https://doi.org/10.1110/ps.062440607
  • Primary Citation of Related Structures:  
    2AIN

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230026, China.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Afadin93Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P55196 (Homo sapiens)
Explore P55196 
Go to UniProtKB:  P55196
PHAROS:  P55196
GTEx:  ENSG00000130396 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55196
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
6-mer peptide from Breakpoint cluster region protein6N/AMutation(s): 0 
EC: 2.7.1
UniProt & NIH Common Fund Data Resources
Find proteins for P11274 (Homo sapiens)
Explore P11274 
Go to UniProtKB:  P11274
PHAROS:  P11274
GTEx:  ENSG00000186716 
Entity Groups  
UniProt GroupP11274
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-07-18
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-03-09
    Changes: Data collection, Database references, Derived calculations