2ZNV

Crystal structure of human AMSH-LP DUB domain in complex with Lys63-linked ubiquitin dimer


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.185 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains

Sato, Y.Yoshikawa, A.Yamagata, A.Mimura, H.Yamashita, M.Ookata, K.Nureki, O.Iwai, K.Komada, M.Fukai, S.

(2008) Nature 455: 358-362

  • DOI: https://doi.org/10.1038/nature07254
  • Primary Citation of Related Structures:  
    2ZNR, 2ZNV

  • PubMed Abstract: 

    Deubiquitinating enzymes (DUBs) remove ubiquitin from conjugated substrates to regulate various cellular processes. The Zn(2+)-dependent DUBs AMSH and AMSH-LP regulate receptor trafficking by specifically cleaving Lys 63-linked polyubiquitin chains from internalized receptors. Here we report the crystal structures of the human AMSH-LP DUB domain alone and in complex with a Lys 63-linked di-ubiquitin at 1.2 A and 1.6 A resolutions, respectively. The AMSH-LP DUB domain consists of a Zn(2+)-coordinating catalytic core and two characteristic insertions, Ins-1 and Ins-2. The distal ubiquitin interacts with Ins-1 and the core, whereas the proximal ubiquitin interacts with Ins-2 and the core. The core and Ins-1 form a catalytic groove that accommodates the Lys 63 side chain of the proximal ubiquitin and the isopeptide-linked carboxy-terminal tail of the distal ubiquitin. This is the first reported structure of a DUB in complex with an isopeptide-linked ubiquitin chain, which reveals the mechanism for Lys 63-linkage-specific deubiquitination by AMSH family members.


  • Organizational Affiliation

    Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
AMSH-like protease
A, D
178Homo sapiensMutation(s): 1 
EC: 3.1.2.15
UniProt & NIH Common Fund Data Resources
Find proteins for Q96FJ0 (Homo sapiens)
Explore Q96FJ0 
Go to UniProtKB:  Q96FJ0
PHAROS:  Q96FJ0
GTEx:  ENSG00000138134 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96FJ0
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin
B, E
76Mus musculusMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for P0CG50 (Mus musculus)
Explore P0CG50 
Go to UniProtKB:  P0CG50
IMPC:  MGI:98889
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0CG50
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin
C, F
77Mus musculusMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for P0CG50 (Mus musculus)
Explore P0CG50 
Go to UniProtKB:  P0CG50
IMPC:  MGI:98889
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0CG50
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.185 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.089α = 90
b = 97.363β = 97.49
c = 87.894γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-09-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-11-10
    Changes: Database references, Derived calculations
  • Version 1.3: 2023-11-01
    Changes: Data collection, Refinement description