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7N4K

H2-Db presenting "SSLENFRAYV" to Alpha/Beta T cell receptor at 1.85Å 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 and alpha beta tcr

1. Beta 2 microglobulin
['B']
2. chimeric_tcr_alpha
['D']
3. chimeric_tcr_beta
['E']
4. Class I alpha
H2-Db
['A']
6. Peptide
SSLENFRAYV
['C']

Species


Locus / Allele group


Publication

Covalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus.

Szeto C, Zareie P, Wirasinha RC, Zhang JB, Nguyen AT, Riboldi-Tunnicliffe A, La Gruta NL, Gras S, Daley SR
Nat Commun (2022) 13, 4951 [doi:10.1038/s41467-022-32692-4]  [pubmed:35999236

Interactions between a T cell receptor (TCR) and a peptide-major histocompatibility complex (pMHC) ligand are typically mediated by noncovalent bonds. By studying T cells expressing natural or engineered TCRs, here we describe covalent TCR-pMHC interactions that involve a cysteine-cysteine disulfide bond between the TCR and the peptide. By introducing cysteines into a known TCR-pMHC combination, we demonstrate that disulfide bond formation does not require structural rearrangement of the TCR or the peptide. We further show these disulfide bonds still form even when the initial affinity of the TCR-pMHC interaction is low. Accordingly, TCR-peptide disulfide bonds facilitate T cell activation by pMHC ligands with a wide spectrum of affinities for the TCR. Physiologically, this mechanism induces strong Zap70-dependent TCR signaling, which triggers T cell deletion or agonist selection in the thymus cortex. Covalent TCR-pMHC interactions may thus underlie a physiological T cell activation mechanism that has applications in basic immunology and potentially in immunotherapy.

Structure deposition and release

Deposited: 2021-06-04
Released: 2022-07-20
Revised: 2022-08-31

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Decamer (10 amino acids)

Sequence: SSLENFRAYV

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 SER

GLU163
LYS66
GLU63
TYR171
TRP167
PHE33
MET5
TYR159
TYR59
TYR7
P10 VAL

LEU81
ASN80
TRP147
LEU95
TYR84
SER77
THR143
TYR123
LYS146
TRP73
P2 SER

TYR159
TYR7
GLU163
LYS66
GLU63
TYR45
P3 LEU

TYR156
LYS66
GLU9
LEU114
HIS155
GLN97
SER99
TYR159
GLN70
P4 GLU

HIS155
GLY69
GLN65
TYR156
LYS66
GLN70
P5 ASN

GLU9
HIS155
GLN97
PHE74
PHE116
TRP73
GLN70
TYR156
P6 PHE

TRP73
SER150
TYR156
ALA152
HIS155
GLY151
P7 ARG

TRP73
P8 ALA

TRP147
SER150
LYS146
TRP73
P9 TYR

VAL76
TRP73
ASN80
TRP147
SER77
THR143
LYS146
GLN72

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
GLU163
TRP167
TYR171
MET5
TYR59
GLU63
LYS66
TYR7
B Pocket

SER24
VAL34
TYR45
GLU63
LYS66
ALA67
TYR7
GLN70
GLU9
SER99
C Pocket

GLN70
TRP73
PHE74
GLU9
GLN97
D Pocket

LEU114
HIS155
TYR156
TYR159
LEU160
SER99
E Pocket

LEU114
TRP147
ALA152
TYR156
GLN97
F Pocket

PHE116
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
MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD
        70        80        90
WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. chimeric_tcr_alpha
chimeric_tcr_alpha
        10        20        30        40        50        60
KTTQPDSMESTEGETVHLPCSHATISGNEYIYWYRQVPLQGPEYVTHGLQQNTTNSMAFL
        70        80        90       100       110       120
AIASDRKSSTLILPHVSLRDAAVYHCILSGGSNYKLTFGKGTLLTVTPNIQNPDPAVYQL
       130       140       150       160       170       180
RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFA
       190
CANAFNNSIIPEDTFFPSP

3. chimeric_tcr_beta
chimeric_tcr_beta
        10        20        30        40        50        60
DMKVTQMPRYLIKRMGENVLLECGQDMSHETMYWYRQDPGLGLQLIYISYDVDSNSEGDI
        70        80        90       100       110       120
PKGYRVSRKKREHFSLILDSAKTNQTSVYFCASSFGREQYFGPGTRLTVLEDLKNVFPPE
       130       140       150       160       170       180
VAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALN
       190       200       210       220       230
DSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRAD

4. Class I alpha
H2-Db
        10        20        30        40        50        60
GPHSMRYFETAVSRPGLEEPRYISVGYVDNKEFVRFDSDAENPRYEPRAPWMEQEGPEYW
        70        80        90       100       110       120
ERETQKAKGQEQWFRVSLRNLLGYYNQSAGGSHTLQQMSGCDLGSDWRLLRGYLQFAYEG
       130       140       150       160       170       180
RDYIALNEDLKTWTAADMAAQITRRKWEQSGAAEHYKAYLEGECVEWLHRYLKNGNATLL
       190       200       210       220       230       240
RTDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGT
       250       260       270
FQKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWEPP

6. Peptide
SSLENFRAYV


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. 7N4K assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 7N4K assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 7N4K assembly 1  
Peptide only [cif]
  1. 7N4K assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/7n4k

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