5MUG

Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.192 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history


Literature

Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier.

Aeschimann, W.Staats, S.Kammer, S.Olieric, N.Jeckelmann, J.M.Fotiadis, D.Netscher, T.Rimbach, G.Cascella, M.Stocker, A.

(2017) Sci Rep 7: 4970-4970

  • DOI: https://doi.org/10.1038/s41598-017-05148-9
  • Primary Citation of Related Structures:  
    5MUE, 5MUG

  • PubMed Abstract: 

    Vitamin E is one of the most important natural antioxidants, protecting polyunsaturated fatty acids in the membranes of cells. Among different chemical isoforms assimilated from dietary regimes, RRR-α-tocopherol is the only one retained in higher animals. This is possible thanks to α-Tocopherol Transfer Protein (α-TTP), which extracts α-tocopherol from endosomal compartments in liver cells, facilitating its distribution into the body. Here we show that, upon binding to its substrate, α-TTP acquires tendency to aggregation into thermodynamically stable high molecular weight oligomers. Determination of the structure of such aggregates by X-ray crystallography revealed a spheroidal particle formed by 24 protein monomers. Oligomerization is triggered by refolding of the N-terminus. Experiments with cultured cell monolayers demonstrate that the same oligomers are efficiently transported through an endothelial barrier (HUVEC) and not through an epithelial one (Caco-2). Discovery of a human endogenous transport protein with intrinsic capability of crossing endothelial tissues opens to new ways of drug delivery into the brain or other tissues protected by endothelial barriers.


  • Organizational Affiliation

    University of Bern, Department of Chemistry and Biochemistry, Bern, 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
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
SO4
Query on SO4

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

Download Ideal Coordinates CCD File 
F [auth A]ETHANOLAMINE
C2 H7 N O
HZAXFHJVJLSVMW-UHFFFAOYSA-N
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: 2.42 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.192 
  • Space Group: I 4 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 168.259α = 90
b = 168.259β = 90
c = 168.259γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-07-19
    Type: Initial release
  • Version 1.1: 2018-12-05
    Changes: Data collection, Source and taxonomy, Structure summary
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references
  • Version 2.1: 2024-01-17
    Changes: Refinement description
  • Version 2.2: 2024-10-09
    Changes: Structure summary