7RTR

HLA-A*02:01 presenting "YLQPRTFLL" to Alpha/Beta T cell receptor at 2.60Å 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.

Complex type

Class i with peptide and alpha beta tcr

1. Beta 2 microglobulin

['B']

2. Class I alpha
HLA-A*02:01

['A']

3. Peptide
YLQPRTFLL

['C']

4. T cell receptor alpha
TRAV12

['D']

5. T cell receptor beta
TRBV7

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-A / HLA-A*02

Publication

Molecular Basis of a Dominant SARS-CoV-2 Spike-Derived Epitope Presented by HLA-A*02:01 Recognised by a Public TCR.

Szeto C, Nguyen AT, Lobos CA, Chatzileontiadou DSM, Jayasinghe D, Grant EJ, Riboldi-Tunnicliffe A, Smith C, Gras S

Cells (2021) 10, [doi:10.3390/cells10102646] [pubmed:34685626]

The data currently available on how the immune system recognises the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus; however, we lack data on how T cells are able to recognise this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.

Structure deposition and release

Deposited: 2021-08-14

Released: 2021-10-13

Revised: 2021-11-03

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: YLQPRTFLL

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 TYR

TYR7

TYR159

TRP167

TYR171

MET5

THR163

GLU63

LYS66

PHE33

TYR59

P2 LEU

GLU63

MET45

TYR159

TYR7

LYS66

HIS70

VAL67

PHE9

TYR99

P3 GLN

TYR99

TYR159

GLN155

ARG97

HIS114

LEU156

LYS66

HIS70

P4 PRO

LYS66

TYR159

P5 ARG

GLN155

HIS70

P6 THR

ALA69

ARG97

THR73

HIS70

P7 PHE

GLN155

THR73

HIS114

LEU156

ARG97

TRP147

ASP77

TYR116

VAL152

P8 LEU

THR73

VAL76

ASP77

TRP147

LYS146

P9 LEU

TYR116

LEU81

LYS146

THR142

TYR84

THR143

TYR123

ASP77

THR80

TRP147

ILE124

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

ALA159

ALA163

THR167

TRP171

ALA5

ARG59

ASP63

SER66

ARG7

B Pocket

ALA24

THR34

ARG45

ASP63

SER66

GLN67

ARG7

GLU70

LEU9

ARG99

C Pocket

GLU70

ALA73

PRO74

LEU9

THR97

D Pocket

ALA114

ARG155

SER156

ALA159

ALA160

ARG99

E Pocket

ALA114

TYR147

GLU152

SER156

THR97

F Pocket

SER116

TYR123

ASP143

ASP146

TYR147

GLU77

GLY80

PRO81

TRP84

SER95

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-A02:01 IPD-IMGT/HLA* [ipd-imgt:HLA35266]	10 20 30 40 50 60 MAVMAPRTLVLLLSGALALTQTWAGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRF 70 80 90 100 110 120 DSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQ 130 140 150 160 170 180 RMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQL 190 200 210 220 230 240 RAYLEGTCVEWLRRYLENGKETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLT 250 260 270 280 290 300 WQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEP 310 320 330 340 350 360 SSQPTIPIVGIIAGLVLFGAVITGAVVAAVMWRRKSSDRKGGSYSQAASSDSAQGSDVSL TACKV

3. Peptide	YLQPRTFLL

4. T cell receptor alpha T cell receptor alpha TRAV12	10 20 30 40 50 60 QKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMFIYSNGDKEDGR 70 80 90 100 110 120 FTAQLNKASQYVSLLIRDSQPSDSATYLCAVNRDDKIIFGKGTRLHILPNIQNPDPAVYQ 130 140 150 160 170 180 LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDF 190 200 ACANAFNNSIIPEDTFFPSPESS

5. T cell receptor beta T cell receptor beta TRBV7	10 20 30 40 50 60 DTGVSQNPRHKITKRGQNVTFRCDPISEHNRLYWYRQTLGQGPEFLTYFQNEAQLEKSRL 70 80 90 100 110 120 LSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCASSPDIEQYFGPGTRLTVTEDLKNVFPP 130 140 150 160 170 180 EVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPAL 190 200 210 220 230 240 NDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRA D

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]

7RTR assembly 1

Components

MHC Class I alpha chain [cif]

7RTR assembly 1

MHC Class I antigen binding domain (alpha1/alpha2) [cif]

7RTR assembly 1

Peptide only [cif]

7RTR assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/7rtr

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

Protein Data Bank Europe - Coordinate Server
1HHK - HLA-A*02:01 binding LLFGYPVYV at 2.5Å resolution - PDB entry for 1HHK
Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. - PyMol CEALIGN Method - Publication
PyMol - PyMol.org/pymol
Levenshtein distance - Wikipedia entry
Protein Data Bank Europe REST API - Molecules endpoint
3Dmol.js: molecular visualization with WebGL - 3DMol.js - Publication
Protein Data Bank Europe REST API - Publication endpoint
PubMed Central Europe REST API - Articles endpoint

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