5FS7

Crystal structure of the G262S mutant of human apoptosis inducing factor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.181 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structure/Function Relations in Aifm1 Variants Associated with Neurodegenerative Disorders.

Sevrioukova, I.F.

(2016) J Mol Biol 428: 3650

  • DOI: https://doi.org/10.1016/j.jmb.2016.05.004
  • Primary Citation of Related Structures:  
    5FS6, 5FS7, 5FS8, 5FS9

  • PubMed Abstract: 

    The X-linked AIFM1 gene encodes mitochondrial apoptosis-inducing factor (AIF), an FAD-containing and NADH-specific oxidoreductase critically important for energy metabolism and execution of the caspase-independent cell death pathway. Several recently identified mutations in human AIFM1 lead to neurodegenerative disorders varying in severity and onset time. This study was undertaken to structurally and functionally characterize four pathologic variants of human AIF: V243L, G262S, G308E, and G338E. A strong correlation between the mutational effects on the AIF function and clinical phenotype was observed only for the G308E aberration, drastically damaging both the redox properties of AIF and mitochondrial respiration. In contrast, only minimal or mild changes were detected in the structure/function of AIF V243L and G338E, respectively, indicating that a marked decrease in their cellular expression likely triggers the disease. Alterations in the structure and redox activity of AIF G262S, on the other hand, were more severe than could be predicted based on the clinical phenotype. Together, the results of this and previous studies allow to conclude that the phenotypic variability and severity of the AIFM1-related disorders depend on which AIF feature is predominantly affected (i.e., cellular production level, structure, redox or apoptogenic function) and to what extent. Only a drastic decrease in the expression level or/and redox activity of AIF tends to cause an early and severe neurodegeneration, whereas less pronounced changes in the AIF properties could lead to a broad range of slowly progressive neurological disorders.


  • Organizational Affiliation

    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA. Electronic address: sevrioui@uci.edu.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
APOPTOSIS-INDUCING FACTOR 1, MITOCHONDRIAL
A, B
515Homo sapiensMutation(s): 1 
EC: 1.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for O95831 (Homo sapiens)
Explore O95831 
Go to UniProtKB:  O95831
PHAROS:  O95831
GTEx:  ENSG00000156709 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO95831
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FAD
Query on FAD

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
FLAVIN-ADENINE DINUCLEOTIDE
C27 H33 N9 O15 P2
VWWQXMAJTJZDQX-UYBVJOGSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.181 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.41α = 90
b = 114.57β = 90
c = 120.79γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-11
    Type: Initial release
  • Version 1.1: 2016-05-18
    Changes: Database references
  • Version 1.2: 2016-05-25
    Changes: Database references
  • Version 1.3: 2016-09-28
    Changes: Database references
  • Version 1.4: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description