4APO

AIP TPR domain in complex with human Tomm20 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structure of the Tpr Domain of Aip: Lack of Client Protein Interaction with the C-Terminal Alpha-7 Helix of the Tpr Domain of Aip is Sufficient for Pituitary Adenoma Predisposition.

Morgan, R.M.Hernandez-Ramirez, L.C.Trivellin, G.Zhou, L.Roe, S.M.Korbonits, M.Prodromou, C.

(2012) PLoS One 7: 53339

  • DOI: https://doi.org/10.1371/journal.pone.0053339
  • Primary Citation of Related Structures:  
    4AIF, 4APO

  • PubMed Abstract: 

    Mutations of the aryl hydrocarbon receptor interacting protein (AIP) have been associated with familial isolated pituitary adenomas predisposing to young-onset acromegaly and gigantism. The precise tumorigenic mechanism is not well understood as AIP interacts with a large number of independent proteins as well as three chaperone systems, HSP90, HSP70 and TOMM20. We have determined the structure of the TPR domain of AIP at high resolution, which has allowed a detailed analysis of how disease-associated mutations impact on the structural integrity of the TPR domain. A subset of C-terminal α-7 helix (Cα-7h) mutations, R304* (nonsense mutation), R304Q, Q307* and R325Q, a known site for AhR and PDE4A5 client-protein interaction, occur beyond those that interact with the conserved MEEVD and EDDVE sequences of HSP90 and TOMM20. These C-terminal AIP mutations appear to only disrupt client-protein binding to the Cα-7h, while chaperone binding remains unaffected, suggesting that failure of client-protein interaction with the Cα-7h is sufficient to predispose to pituitary adenoma. We have also identified a molecular switch in the AIP TPR-domain that allows recognition of both the conserved HSP90 motif, MEEVD, and the equivalent sequence (EDDVE) of TOMM20.


  • Organizational Affiliation

    Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
AH RECEPTOR-INTERACTING PROTEIN
A, B
165Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for O00170 (Homo sapiens)
Explore O00170 
Go to UniProtKB:  O00170
PHAROS:  O00170
GTEx:  ENSG00000110711 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO00170
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
MITOCHONDRIAL IMPORT RECEPTOR SUBUNIT TOM20 HOMOLOGC [auth D],
D [auth E]
6Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15388 (Homo sapiens)
Explore Q15388 
Go to UniProtKB:  Q15388
PHAROS:  Q15388
GTEx:  ENSG00000173726 
Entity Groups  
UniProt GroupQ15388
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.184 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.2α = 90
b = 106.82β = 100.85
c = 68.47γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-01-23
    Type: Initial release
  • Version 1.1: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description