2NYT

The APOBEC2 Crystal Structure and Functional Implications for AID


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.246 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The APOBEC-2 crystal structure and functional implications for the deaminase AID.

Prochnow, C.Bransteitter, R.Klein, M.G.Goodman, M.F.Chen, X.S.

(2007) Nature 445: 447-451

  • DOI: https://doi.org/10.1038/nature05492
  • Primary Citation of Related Structures:  
    2NYT

  • PubMed Abstract: 

    APOBEC-2 (APO2) belongs to the family of apolipoprotein B messenger RNA-editing enzyme catalytic (APOBEC) polypeptides, which deaminates mRNA and single-stranded DNA. Different APOBEC members use the same deamination activity to achieve diverse human biological functions. Deamination by an APOBEC protein called activation-induced cytidine deaminase (AID) is critical for generating high-affinity antibodies, and deamination by APOBEC-3 proteins can inhibit retrotransposons and the replication of retroviruses such as human immunodeficiency virus and hepatitis B virus. Here we report the crystal structure of APO2. APO2 forms a rod-shaped tetramer that differs markedly from the square-shaped tetramer of the free nucleotide cytidine deaminase, with which APOBEC proteins share considerable sequence homology. In APO2, two long alpha-helices of a monomer structure prevent the formation of a square-shaped tetramer and facilitate formation of the rod-shaped tetramer via head-to-head interactions of two APO2 dimers. Extensive sequence homology among APOBEC family members allows us to test APO2 structure-based predictions using AID. We show that AID deamination activity is impaired by mutations predicted to interfere with oligomerization and substrate access. The structure suggests how mutations in patients with hyper-IgM-2 syndrome inactivate AID, resulting in defective antibody maturation.


  • Organizational Affiliation

    Molecular and Computational Biology, University of Southern California Los Angeles, California 90089, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Probable C->U-editing enzyme APOBEC-2
A, B, C, D
190Homo sapiensMutation(s): 0 
Gene Names: APOBEC2
EC: 3.5.4
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y235 (Homo sapiens)
Explore Q9Y235 
Go to UniProtKB:  Q9Y235
PHAROS:  Q9Y235
GTEx:  ENSG00000124701 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y235
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.246 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.841α = 90
b = 89.41β = 90
c = 245.77γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SHELXDphasing
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-01-09
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-27
    Changes: Data collection, Database references, Derived calculations