3NTW

Structure of the MLLE domain of EDD in complex with a PAM2 peptide from Paip1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.230 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The MLLE domain of the ubiquitin ligase UBR5 binds to its catalytic domain to regulate substrate binding.

Munoz-Escobar, J.Matta-Camacho, E.Kozlov, G.Gehring, K.

(2015) J Biol Chem 290: 22841-22850

  • DOI: https://doi.org/10.1074/jbc.M115.672246
  • Primary Citation of Related Structures:  
    3NTW

  • PubMed Abstract: 

    E3 ubiquitin ligases catalyze the transfer of ubiquitin from an E2-conjugating enzyme to a substrate. UBR5, homologous to the E6AP C terminus (HECT)-type E3 ligase, mediates the ubiquitination of proteins involved in translation regulation, DNA damage response, and gluconeogenesis. In addition, UBR5 functions in a ligase-independent manner by prompting protein/protein interactions without ubiquitination of the binding partner. Despite recent functional studies, the mechanisms involved in substrate recognition and selective ubiquitination of its binding partners remain elusive. The C terminus of UBR5 harbors the HECT catalytic domain and an adjacent MLLE domain. MLLE domains mediate protein/protein interactions through the binding of a conserved peptide motif, termed PAM2. Here, we characterize the binding properties of the UBR5 MLLE domain to PAM2 peptides from Paip1 and GW182. The crystal structure with a Paip1 PAM2 peptide reveals the network of hydrophobic and ionic interactions that drive binding. In addition, we identify a novel interaction of the MLLE domain with the adjacent HECT domain mediated by a PAM2-like sequence. Our results confirm the role of the MLLE domain of UBR5 in substrate recruitment and suggest a potential role in regulating UBR5 ligase activity.


  • Organizational Affiliation

    From the Department of Biochemistry, Groupe de Recherche Axé sur la Structure des Protéines, McGill University, Montréal, Québec H3G 0B1, Canada.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
E3 ubiquitin-protein ligase UBR5
A, C
65Rattus norvegicusMutation(s): 0 
Gene Names: Ubr5Dd5EddEdd1Hyd
EC: 6.3.2
UniProt
Find proteins for Q62671 (Rattus norvegicus)
Explore Q62671 
Go to UniProtKB:  Q62671
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ62671
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Polyadenylate-binding protein-interacting protein 1
B, D
22N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9H074 (Homo sapiens)
Explore Q9H074 
Go to UniProtKB:  Q9H074
PHAROS:  Q9H074
GTEx:  ENSG00000172239 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9H074
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.230 
  • Space Group: P 64 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.794α = 90
b = 95.794β = 90
c = 82.936γ = 120
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-07-06
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-10-03
    Changes: Data collection, Database references
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Refinement description