6ZPD

gamma-tocopherol transfer protein


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.24 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Engineering of a functional gamma-tocopherol transfer protein.

Aeschimann, W.Kammer, S.Staats, S.Schneider, P.Schneider, G.Rimbach, G.Cascella, M.Stocker, A.

(2020) Redox Biol 38: 101773-101773

  • DOI: https://doi.org/10.1016/j.redox.2020.101773
  • Primary Citation of Related Structures:  
    6ZPD

  • PubMed Abstract: 

    α-tocopherol transfer protein (TTP) was previously reported to self-aggregate into 24-meric spheres (α-TTP S ) and to possess transcytotic potency across mono-layers of human umbilical vein endothelial cells (HUVECs). In this work, we describe the characterisation of a functional TTP variant with its vitamer selectivity shifted towards γ-tocopherol. The shift was obtained by introducing an alanine to leucine substitution into the substrate-binding pocket at position 156 through site directed mutagenesis. We report here the X-ray crystal structure of the γ-tocopherol specific particle (γ-TTP S ) at 2.24 Å resolution. γ-TTP S features full functionality compared to its α-tocopherol specific parent including self-aggregation potency and transcytotic activity in trans-well experiments using primary HUVEC cells. The impact of the A156L mutation on TTP function is quantified in vitro by measuring the affinity towards γ-tocopherol through micro-differential scanning calorimetry and by determining its ligand-transfer activity. Finally, cell culture experiments using adherently grown HUVEC cells indicate that the protomers of γ-TTP, in contrast to α-TTP, do not counteract cytokine-mediated inflammation at a transcriptional level. Our results suggest that the A156L substitution in TTP is fully functional and has the potential to pave the way for further experiments towards the understanding of α-tocopherol homeostasis in humans.


  • Organizational Affiliation

    University of Bern, Department of Chemistry and Biochemistry, Bern, 3012, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-tocopherol transfer protein231Homo sapiensMutation(s): 0 
Gene Names: TTPATPP1
UniProt & NIH Common Fund Data Resources
Find proteins for P49638 (Homo sapiens)
Explore P49638 
Go to UniProtKB:  P49638
PHAROS:  P49638
GTEx:  ENSG00000137561 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49638
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
VIV (Subject of Investigation/LOI)
Query on VIV

Download Ideal Coordinates CCD File 
B [auth A](2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL
C29 H50 O2
GVJHHUAWPYXKBD-IEOSBIPESA-N
TRS
Query on TRS

Download Ideal Coordinates CCD File 
F [auth A]2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
CL
Query on CL

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.24 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 
  • Space Group: I 4 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 167.687α = 90
b = 167.687β = 90
c = 167.687γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Swiss National Science FoundationSwitzerland31003A_156419

Revision History  (Full details and data files)

  • Version 1.0: 2020-12-02
    Type: Initial release
  • Version 1.1: 2024-01-31
    Changes: Data collection, Database references, Refinement description
  • Version 1.2: 2024-10-16
    Changes: Structure summary