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


7EU2

HLA-A*02:01 binding "KIADYNYKL" at 2.80Å 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', 'E']
2. Class I alpha
HLA-A*02:01
['A', 'D']
3. Peptide
KIADYNYKL
['C', 'F']

Species

Locus / Allele group

HLA-A / HLA-A*02

Publication

Profiling CD8+ T��cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants.

Zhang H, Deng S, Ren L, Zheng P, Hu X, Jin T, Tan X
Cell Rep (2021) 36, 109708 [doi:10.1016/j.celrep.2021.109708]  [pubmed:34506741] 

Cellular immunity is important in determining the disease severity of COVID-19 patients. However, current understanding of SARS-CoV-2 epitopes mediating cellular immunity is limited. Here we apply T-Scan, a recently developed method, to identify CD8+ T cell epitopes from COVID-19 patients of four major HLA-A alleles. Several identified epitopes are conserved across human coronaviruses, which might mediate pre-existing cellular immunity to SARS-CoV-2. In addition, we identify and validate four epitopes that were mutated in the newly circulating variants, including the Delta variant. The mutations significantly reduce T cell responses to the epitope peptides in convalescent and vaccinated samples. We further determine the crystal structure of HLA-A∗02:01/HLA-A∗24:02 in complex with the epitope KIA_S/NYN_S, respectively, which reveals the importance of K417 and L452 of the spike protein for binding to HLA. Our data suggest that evading cellular immunity might contribute to the increased transmissibility and disease severity associated with the new SARS-CoV-2 variants.

Structure deposition and release

Deposited: 2021-05-15
Released: 2021-08-25
Revised: 2022-03-09

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: KIADYNYKL

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 LYS

TYR171
THR163
TYR59
GLU63
LYS66
MET5
PHE33
TYR159
TRP167
TYR7
 P2 ILE

TYR159
TYR7
HIS70
MET45
TYR99
VAL67
PHE9
GLU63
LYS66
 P3 ALA

LYS66
HIS70
TYR99
TYR159
 P4 ASP

TYR159
ARG65
LYS66
 P5 TYR

GLN155
 P6 ASN

THR73
LYS66
ARG97
HIS70
ALA69
 P7 TYR

THR73
ASP77
TRP147
VAL152
GLN155
TYR116
 P8 LYS

GLN72
THR143
VAL76
TRP147
ASP77
THR73
 P9 LEU

TYR123
LYS146
ASP77
TYR116
THR143
TRP147
THR80
ILE124
TYR84
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

GLU159
ALA163
GLY167
GLU171
ASP5
GLN59
GLU63
ASP66
SER7
B Pocket

GLU24
ASP34
ALA45
GLU63
ASP66
GLY67
SER7
ARG70
SER9
THR99
C Pocket

ARG70
LYS73
ALA74
SER9
SER97
D Pocket

PHE114
ALA155
HIS156
GLU159
GLN160
THR99
E Pocket

PHE114
THR147
TRP152
HIS156
SER97
F Pocket

ARG116
TYR123
MET143
GLN146
THR147
GLN77
ARG80
VAL81
GLY84
ALA95

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
GSVDMIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLS
        70        80        90       100
FSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM
2. Class I alpha
HLA-A*02:01
IPD-IMGT/HLA
[ipd-imgt:HLA35266]
        10        20        30        40        50        60
MNSVDGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQE
        70        80        90       100       110       120
GPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQ
       130       140       150       160       170       180
YAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENG
       190       200       210       220       230       240
KETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRP
       250       260       270       280       290       300
AGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEPGSGLNDIFEAQKIEWHAAA

LEHHHHHH
3. Peptide
KIADYNYKL

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. 7EU2 assembly 1  
  2. 7EU2 assembly 2  

Components

MHC Class I alpha chain [cif]
  1. 7EU2 assembly 1  
  2. 7EU2 assembly 2  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 7EU2 assembly 1  
  2. 7EU2 assembly 2  
Peptide only [cif]
  1. 7EU2 assembly 1  
  2. 7EU2 assembly 2  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/7eu2

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.