Alpha This is a work in progress and may change. Your feedback is very welcome.
  


3SKO

HLA-B*08:01 binding "FLRGRAYGL" at 1.60Å resolution

Data provenance

Structure downloaded from PDB Europe using the Coordinate Server. Aligned to residues 1-180 of 1HHK2 using the CEALIGN3 function of PyMol4. Chain assigment using a Levenshtein distance5 method using data from the PDBe REST API6. Organism data from PDBe REST API. Data for both of these operations from the Molecules endpoint. Structure visualised with 3DMol7.

Information sections

Complex type

Class i with peptide

1. Beta 2 microglobulin
['B']
2. Class I alpha
HLA-B*08:01
['A']
3. Peptide
FLRGRAYGL
['C']

Species

Locus / Allele group

HLA-B / HLA-B*08

Publication

A structural basis for varied ���� TCR usage against an immunodominant EBV antigen restricted to a HLA-B8 molecule.

Gras S, Wilmann PG, Chen Z, Halim H, Liu YC, Kjer-Nielsen L, Purcell AW, Burrows SR, McCluskey J, Rossjohn J
J. Immunol. (2012) 188, 311-21 [doi:10.4049/jimmunol.1102686]  [pubmed:22140258] 

EBV is a ubiquitous and persistent human pathogen, kept in check by the cytotoxic T cell response. In this study, we investigated how three TCRs, which differ in their T cell immunodominance hierarchies and gene usage, interact with the same EBV determinant (FLRGRAYGL), bound to the same Ag-presenting molecule, HLA-B8. We found that the three TCRs exhibit differing fine specificities for the viral Ag. Further, via structural and biophysical approaches, we demonstrated that the viral Ag provides the greatest energetic contribution to the TCR-peptide-HLA interaction, while focusing on a few adjacent HLA-based interactions to further tune fine-specificity requirements. Thus, the TCR engages the peptide-HLA with the viral Ag as the main glue, such that neighboring TCR-MHC interactions are recruited as a supportive adhesive. Collectively, we provide a portrait of how the host's adaptive immune response differentially engages a common viral Ag.

Structure deposition and release

Deposited: 2011-06-22
Released: 2012-02-29
Revised: 2012-08-01

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Nonamer (9 amino acids)

Sequence: FLRGRAYGL

Interactive view
Cutaway side view (static)
Surface top view (static - coloured by atom property)
Cutaway top view (static)

Data provenance

MHC:peptide complexes are visualised using PyMol. The peptide is superimposed on a consistent cutaway slice of the MHC binding cleft (displayed as a grey mesh) which best indicates the binding pockets for the P1/P5/PC positions (side view - pockets A, E, F) and for the P2/P3/PC-2 positions (top view - pockets B, C, D). In some cases peptides will use a different pocket for a specific peptide position (atypical anchoring). On some structures the peptide may appear to sterically clash with a pocket. This is an artefact of picking a standardised slice of the cleft and overlaying the peptide.

Peptide neighbours

P1 PHE

ASN63
TYR171
MET5
TRP167
TYR159
TYR59
TYR7
PHE33
ARG62
THR163
 P2 LEU

TYR159
TYR7
ASN70
TYR99
SER24
ASN63
ALA66
PHE36
PHE67
 P3 ARG

ALA66
TYR159
GLN155
ASN70
TYR99
ASP156
 P4 GLY

ALA66
THR69
ASN70
 P5 ARG

ASN114
PHE22
SER97
THR73
ASP9
ASP74
TYR116
THR69
ASN70
TYR99
 P6 ALA

THR69
THR73
 P7 TYR

TRP147
ALA150
VAL152
GLN155
THR73
 P8 GLY

SER77
THR73
TRP147
THR143
 P9 LEU

LEU81
TRP147
TYR123
TYR116
ASN80
TYR84
SER77
LEU95
LYS146
THR143

Colour key

Aromatic Hydrophobic Acidic Basic Neutral/polar

Data provenance

Neighbours are calculated by finding residues with atoms within 5Å of each other using BioPython Neighboursearch module. The list of neighbours is then sorted and filtered to inlcude only neighbours where between the peptide and the MHC Class I alpha chain.

Colours selected to match the YRB scheme. [https://www.frontiersin.org/articles/10.3389/fmolb.2015.00056/full]

Binding cleft pockets


Peptide sidechain binding pockets (static)
Peptide terminii and backbone binding residues (static)
A Pocket

TYR159
THR163
TRP167
TYR171
MET5
TYR59
ASN63
ALA66
TYR7
B Pocket

SER24
VAL34
GLU45
ASN63
ALA66
PHE67
TYR7
ASN70
ASP9
TYR99
C Pocket

ASN70
THR73
ASP74
ASP9
SER97
D Pocket

ASN114
GLN155
ASP156
TYR159
LEU160
TYR99
E Pocket

ASN114
TRP147
VAL152
ASP156
SER97
F Pocket

TYR116
TYR123
THR143
LYS146
TRP147
SER77
ASN80
LEU81
TYR84
LEU95

Colour key

Binds N-terminus Binds P1 backbone Binds P2 backbone Binds PC-1 backbone Binds C-terminus

Data provenance

N-/C-terminus and peptide backbone binding residues are assigned according to previously published information and pockets are assigned according to an adaptation of a previously published set of residues. All numbering is currently that of the 'canonical' structures of human and mouse MHC Class I molecules.

Chain sequences

1. Beta 2 microglobulin
Beta 2 microglobulin
        10        20        30        40        50        60
MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD
        70        80        90
WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM
2. Class I alpha
HLA-B*08:01
IPD-IMGT/HLA
[ipd-imgt:HLA34671]
        10        20        30        40        50        60
GSHSMRYFDTAMSRPGRGEPRFISVGYVDDTQFVRFDSDAASPREEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DRNTQAFKTNTQTDRESLRNLRGYYNQSEAGSHTLQSMYGCDVGPDGRLLRGHNQYAYDG
       130       140       150       160       170       180
KDYIALNEDLRSWTAADTAAQITQRKWEAARVAEQDRAYLEGTCVEWLRRYLENGKDTLE
       190       200       210       220       230       240
RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEPS
3. Peptide
FLRGRAYGL

Data provenance

Sequences are retrieved via the Uniprot method of the RSCB REST API. Sequences are then compared to those derived from the PDB file and matched against sequences retrieved from the IPD-IMGT/HLA database for human sequences, or the IPD-MHC database for other species. Mouse sequences are matched against FASTA files from Uniprot. Sequences for the mature extracellular protein (signal petide and cytoplasmic tail removed) are compared to identical length sequences from the datasources mentioned before using either exact matching or Levenshtein distance based matching.

Downloadable data

Data can be downloaded to your local machine from the links below.
Clicking on the clipboard icon will copy the url for the data to your clipboard.
This can then be used to load the structure/data directly from the url into an application like PyMol (for 3D structures) using the load command:
   e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif
or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.
Please take note of the data license. Using data from this site assumes that you have read and will comply with the license.

Complete structures

Aligned structures [cif]
  1. 3SKO assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 3SKO assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 3SKO assembly 1  
Peptide only [cif]
  1. 3SKO assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/3sko

Data license

The data above is made available under a Creative Commons CC-BY 4.0 license. This means you can copy, remix, transform, build upon and redistribute the material, but you must give appropriate credit, provide a link to the license, and indicate if changes were made.
If you use any data downloaded from this site in a publication, please cite 'https://www.histo.fyi/'. A preprint is in preparation.

Footnotes


Creative Commons Licence
This work is licensed under a Creative Commons Attribution 4.0 International License.