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4PRB

HLA-B*35:08 binding "HPVAEADYFEY" at 1.75Å 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*35:08
['A']
3. Peptide
HPVAEADYFEY
['C']

Species


Locus / Allele group


Publication

A Molecular Basis for the Interplay between T Cells, Viral Mutants, and Human Leukocyte Antigen Micropolymorphism.

Liu YC, Chen Z, Neller MA, Miles JJ, Purcell AW, McCluskey J, Burrows SR, Rossjohn J, Gras S
J. Biol. Chem. (2014) 289, 16688-16698 [doi:10.1074/jbc.M114.563502]  [pubmed:24759101

Mutations within T cell epitopes represent a common mechanism of viral escape from the host protective immune response. The diverse T cell repertoire and the extensive human leukocyte antigen (HLA) polymorphism across populations is the evolutionary response to viral mutation. However, the molecular basis underpinning the interplay between HLA polymorphism, the T cell repertoire, and viral escape is unclear. Here we investigate the T cell response to a HLA-B*35:01- and HLA-B*35:08-restricted (407)HPVGEADYFEY(417) epitope from Epstein-Barr virus and naturally occurring variants at positions 4 and 5 thereof. Each viral variant differently impacted on the epitope's flexibility and conformation when bound to HLA-B*35:08 or HLA-B*35:01. We provide a molecular basis for understanding how the single residue polymorphism that discriminates between HLA-B*35:01/08 profoundly impacts on T cell receptor recognition. Surprisingly, one viral variant (P5-Glu to P5-Asp) effectively changed restriction preference from HLA-B*35:01 to HLA-B*35:08. Collectively, our study portrays the interplay between the T cell response, viral escape, and HLA polymorphism, whereby HLA polymorphism enables altered presentation of epitopes from different strains of Epstein-Barr virus.

Structure deposition and release

Deposited: 2014-03-05
Released: 2014-04-16
Revised: 2017-11-22

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Undecamer (11 amino acids)

Sequence: HPVAEADYFEY

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 HIS

TRP167
PHE33
ARG62
TYR171
TYR7
ASN63
MET5
TYR159
TYR59
ILE66
P10 GLU

GLU76
SER77
ASN80
LYS146
TRP147
P11 TYR

ASN80
SER116
LEU81
SER77
ILE124
TYR84
THR143
LYS146
TRP147
ILE95
TYR123
GLN96
TYR74
ARG97
P2 PRO

ASN63
TYR7
TYR159
ILE66
TYR99
PHE67
TYR9
P3 VAL

TYR99
ARG156
TYR159
ILE66
GLN155
ARG97
TYR9
P4 ALA

ILE66
GLN155
ARG156
ARG62
P5 GLU

ASN70
ARG156
ARG97
TYR9
P9 PHE

VAL152
TYR74
ARG97
TRP147
ARG156
THR73
SER77

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
LEU163
TRP167
TYR171
MET5
TYR59
ASN63
ILE66
TYR7
B Pocket

ALA24
VAL34
THR45
ASN63
ILE66
PHE67
TYR7
ASN70
TYR9
TYR99
C Pocket

ASN70
THR73
TYR74
TYR9
ARG97
D Pocket

ASP114
GLN155
ARG156
TYR159
LEU160
TYR99
E Pocket

ASP114
TRP147
VAL152
ARG156
ARG97
F Pocket

SER116
TYR123
THR143
LYS146
TRP147
SER77
ASN80
LEU81
TYR84
ILE95

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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-B*35:08
IPD-IMGT/HLA
[ipd-imgt:HLA31926]
        10        20        30        40        50        60
GSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DRNTQIFKTNTQTYRESLRNLRGYYNQSEAGSHIIQRMYGCDLGPDGRLLRGHDQSAYDG
       130       140       150       160       170       180
KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQRRAYLEGLCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RADPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide
HPVAEADYFEY


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

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Complete structures

Aligned structures [cif]
  1. 4PRB assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 4PRB assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 4PRB assembly 1  
Peptide only [cif]
  1. 4PRB assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/4prb

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