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7F4W

HLA-A*24:02 binding "NYNYLYRLF" at 2.90Å 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', 'D']
2. Class I alpha
HLA-A*24:02
['A', 'C']
3. Peptide
NYNYLYRLF
['E', 'F']

Species

Locus / Allele group

HLA-A / HLA-A*24

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: 2021-06-21
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: NYNYLYRLF

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 ASN

GLU63
LYS66
TYR171
PHE33
MET5
ARG170
TYR159
TYR59
TYR7
CYS164
THR163
GLY167
 P2 TYR

TYR7
HIS70
GLU63
LYS66
SER9
MET45
PHE99
ALA24
VAL67
TYR159
PHE22
 P3 ASN

MET97
PHE99
TYR159
LYS66
HIS114
GLN156
 P4 TYR

TYR159
LYS66
THR163
GLN155
ALA158
 P5 LEU

GLN155
TYR159
GLN156
 P6 TYR

HIS70
LYS66
VAL67
ALA69
THR73
 P7 ARG

VAL152
ASN77
ALA150
THR73
TRP147
 P8 LEU

ASN77
THR143
GLU76
LYS146
THR73
TRP147
 P9 PHE

ASN77
ILE80
LEU95
TYR84
THR143
TYR123
LYS146
ILE124
TYR116
TRP147
ALA81

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
ASP171
ASP5
GLN59
GLU63
ASP66
SER7
B Pocket

GLU24
ASP34
ALA45
GLU63
ASP66
GLU67
SER7
GLY70
SER9
THR99
C Pocket

GLY70
LYS73
ALA74
SER9
SER97
D Pocket

PHE114
ALA155
HIS156
GLU159
GLN160
THR99
E Pocket

PHE114
ILE147
TRP152
HIS156
SER97
F Pocket

ARG116
TYR123
MET143
GLN146
ILE147
GLN77
ARG80
GLU81
ARG84
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
VDMIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFS
        70        80        90       100
KDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM
2. Class I alpha
HLA-A*24:02
IPD-IMGT/HLA
[ipd-imgt:HLA34790]
        10        20        30        40        50        60
MNSVDGSHSMRYFSTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQE
        70        80        90       100       110       120
GPEYWDEETGKVKAHSQTDRENLRIALRYYNQSEAGSHTLQMMFGCDVGSDGRFLRGYHQ
       130       140       150       160       170       180
YAYDGKDYIALKEDLRSWTAADMAAQITKRKWEAAHVAEQQRAYLEGTCVDGLRRYLENG
       190       200       210       220       230       240
KETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRP
       250       260       270       280       290       300
AGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEPGSGLNDIFEAQKIEWHAAA

LEHHHHHH
3. Peptide
NYNYLYRLF

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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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. 7F4W assembly 1  
  2. 7F4W assembly 2  

Components

MHC Class I alpha chain [cif]
  1. 7F4W assembly 1  
  2. 7F4W assembly 2  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 7F4W assembly 1  
  2. 7F4W assembly 2  
Peptide only [cif]
  1. 7F4W assembly 1  
  2. 7F4W assembly 2  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/7f4w

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.