1R4N

APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex with ATP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.60 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.269 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1.

Walden, H.Podgorski, M.S.Huang, D.T.Miller, D.W.Howard, R.J.Minor, D.L.Holton, J.M.Schulman, B.A.

(2003) Mol Cell 12: 1427-1437

  • DOI: https://doi.org/10.1016/s1097-2765(03)00452-0
  • Primary Citation of Related Structures:  
    1R4M, 1R4N

  • PubMed Abstract: 

    E1 enzymes initiate ubiquitin-like protein (ubl) transfer cascades by catalyzing adenylation of the ubl's C terminus. An E1's selectivity for its cognate ubl is essential because the E1 subsequently coordinates the ubl with its correct downstream pathway. We report here the structure of the 120 kDa quaternary complex between human APPBP1-UBA3, a heterodimeric E1, its ubl NEDD8, and ATP. The E1 selectively recruits NEDD8 through a bipartite interface, involving a domain common to all ubl activating enzymes including bacterial ancestors, and also eukaryotic E1-specific sequences. By modeling ubiquitin into the NEDD8 binding site and performing mutational analysis, we identify a single conserved arginine in APPBP1-UBA3 that acts as a selectivity gate, preventing misactivation of ubiquitin by NEDD8's E1. NEDD8 residues that interact with E1 correspond to residues in ubiquitin important for binding the proteasome and other ubiquitin-interacting proteins, suggesting that the conjugation and recognition machineries have coevolved for each specific ubl.


  • Organizational Affiliation

    Departments of Structural Biology and Genetics/Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
amyloid beta precursor protein-binding protein 1A,
D [auth C],
G [auth E],
J [auth G]
529Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q13564 (Homo sapiens)
Explore Q13564 
Go to UniProtKB:  Q13564
PHAROS:  Q13564
GTEx:  ENSG00000159593 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13564
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
ubiquitin-activating enzyme E1CB,
E [auth D],
H [auth F],
K [auth H]
431Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for Q8TBC4 (Homo sapiens)
Explore Q8TBC4 
Go to UniProtKB:  Q8TBC4
PHAROS:  Q8TBC4
GTEx:  ENSG00000144744 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8TBC4
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin-like protein NEDD8C [auth I],
F [auth J],
I [auth K],
L
76Homo sapiensMutation(s): 0 
Gene Names: NEDD8
UniProt & NIH Common Fund Data Resources
Find proteins for Q15843 (Homo sapiens)
Explore Q15843 
Go to UniProtKB:  Q15843
PHAROS:  Q15843
GTEx:  ENSG00000129559 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15843
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.60 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.269 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 135α = 90
b = 197.9β = 90
c = 211γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
HKL-2000data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-12-23
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-02-01
    Changes: Structure summary
  • Version 1.4: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.5: 2023-08-23
    Changes: Data collection, Refinement description