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4QRS

HLA-B*08:01 binding "ELKRKMIYM" at 1.40Å 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
ELKRKMIYM
['C']

Species


Locus / Allele group


Publication

Molecular imprint of exposure to naturally occurring genetic variants of human cytomegalovirus on the T cell repertoire.

Smith C, Gras S, Brennan RM, Bird NL, Valkenburg SA, Twist KA, Burrows JM, Miles JJ, Chambers D, Bell S, Campbell S, Kedzierska K, Burrows SR, Rossjohn J, Khanna R
Sci Rep (2014) 4, 3993 [doi:10.1038/srep03993]  [pubmed:24509977

Exposure to naturally occurring variants of herpesviruses in clinical settings can have a dramatic impact on anti-viral immunity. Here we have evaluated the molecular imprint of variant peptide-MHC complexes on the T-cell repertoire during human cytomegalovirus (CMV) infection and demonstrate that primary co-infection with genetic variants of CMV was coincident with development of strain-specific T-cell immunity followed by emergence of cross-reactive virus-specific T-cells. Cross-reactive CMV-specific T cells exhibited a highly conserved public T cell repertoire, while T cells directed towards specific genetic variants displayed oligoclonal repertoires, unique to each individual. T cell recognition foot-print and pMHC-I structural analyses revealed that the cross-reactive T cells accommodate alterations in the pMHC complex with a broader foot-print focussing on the core of the peptide epitope. These findings provide novel molecular insight into how infection with naturally occurring genetic variants of persistent human herpesviruses imprints on the evolution of the anti-viral T-cell repertoire.

Structure deposition and release

Deposited: 2014-07-02
Released: 2014-12-10
Revised: 2019-07-17

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: ELKRKMIYM

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 GLU

PHE33
ARG62
TRP167
MET5
TYR159
THR163
ILE66
TYR7
TYR99
TYR59
ASN63
TYR171
P2 LEU

ILE66
ASN63
SER24
PHE67
PHE36
TYR159
TYR7
ASN70
TYR99
P3 LYS

TYR159
ILE66
ASN114
ASN70
TYR99
TYR116
ASP156
P4 ARG

ASN70
ASP156
ILE66
ARG62
P5 LYS

ASN70
TYR99
ASP74
THR69
SER97
TYR116
THR73
ASP9
PHE22
P6 MET

THR69
THR73
GLN155
P7 ILE

ALA150
THR73
SER77
TRP147
LYS146
VAL152
P8 TYR

GLU76
ASN80
LYS146
THR73
SER77
TRP147
GLN72
P9 MET

TRP147
LEU95
ILE142
ASP74
THR143
TYR116
TYR84
SER77
TYR123
ASN80
LYS146
ILE124
LEU81

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
ILE66
TYR7
B Pocket

SER24
VAL34
GLU45
ASN63
ILE66
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
MGQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD
        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
DRNTQIFKTNTQTDRESLRNLRGYYNQSEAGSHTLQSMYGCDVGPDGRLLRGHNQYAYDG
       130       140       150       160       170       180
KDYIALNEDLRSWTAADTAAQITQRKWEAARVAEQDRAYLEGTCVEWLRRYLENGKDTLE
       190       200       210       220       230       240
RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide
ELKRKMIYM


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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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. 4QRS assembly 1  

Components

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

Derived data

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

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