6SS7

Human Leukocyte Antigen Class I A02 Carrying LLWAGPMAV


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.304 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.230 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Identification of a superagonist variant of the immunodominant Yellow fever virus epitope NS4b214-222by combinatorial peptide library screening.

Bovay, A.Zoete, V.Rizkallah, P.J.Beck, K.Delbreil, P.Speiser, D.E.Cole, D.K.Fuertes Marraco, S.A.

(2020) Mol Immunol 125: 43-50

  • DOI: https://doi.org/10.1016/j.molimm.2020.06.025
  • Primary Citation of Related Structures:  
    6SS7, 6SS8, 6SS9, 6SSA

  • PubMed Abstract: 

    The CD8 T cell response to the HLA-A2-restricted epitope LLWNGPMAV (LLW) of the non-structural protein 4b of Yellow Fever Virus (YFV) is remarkably immunodominant, highly prevalent and powerful in YFV-vaccinated humans. Here we used a combinatorial peptide library screening in the context of an A2/LLW-specific CD8 T cell clone to identify a superagonist that features a methionine to isoleucine substitution at position 7. Based on in silico modeling, the functional enhancement of this LLW-7I mutation was associated with alterations in the structural dynamics of the peptide in the major histocompatibility complex (pMHC) binding with the T cell receptor (TCR). While the TCR off-rate of LLW-7I pMHC is comparable to the wild type peptide, the rigidity of the 7I peptide seems to confer less entropy loss upon TCR binding. This LLW-7I superagonist is an example of improved functionality in human CD8 T cells associated with optimized ligand rigidity for TCR binding and not with changes in TCR:pMHC off-rate kinetics.


  • Organizational Affiliation

    Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, A-2 alpha chain
A, D
276Homo sapiensMutation(s): 0 
Gene Names: HLA-AHLAA
UniProt & NIH Common Fund Data Resources
Find proteins for P04439 (Homo sapiens)
Explore P04439 
Go to UniProtKB:  P04439
PHAROS:  P04439
GTEx:  ENSG00000206503 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04439
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin
B, E
100Homo sapiensMutation(s): 0 
Gene Names: B2MCDABP0092HDCMA22P
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
Explore P61769 
Go to UniProtKB:  P61769
PHAROS:  P61769
GTEx:  ENSG00000166710 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61769
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
LEU-LEU-TRP-ALA-GLY-PRO-MET-ALA-VAL
C, F
9Yellow fever virusMutation(s): 0 
UniProt
Find proteins for P03314 (Yellow fever virus (strain 17D vaccine))
Explore P03314 
Go to UniProtKB:  P03314
Entity Groups  
UniProt GroupP03314
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
AA [auth D]
BA [auth D]
EA [auth E]
FA [auth E]
J [auth A]
AA [auth D],
BA [auth D],
EA [auth E],
FA [auth E],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
T [auth B],
Z [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
CA [auth D]
DA [auth D]
N [auth A]
O [auth A]
P [auth A]
CA [auth D],
DA [auth D],
N [auth A],
O [auth A],
P [auth A],
U [auth B],
V [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
H [auth A]
I [auth A]
Q [auth B]
R [auth B]
S [auth B]
H [auth A],
I [auth A],
Q [auth B],
R [auth B],
S [auth B],
X [auth D],
Y [auth D]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
G [auth A],
W [auth D]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.304 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.230 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 117.56α = 90
b = 169.25β = 90
c = 49.07γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
Aimlessdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Swiss National Science FoundationSwitzerland310030B_179570

Revision History  (Full details and data files)

  • Version 1.0: 2020-07-15
    Type: Initial release
  • Version 1.1: 2020-07-22
    Changes: Database references