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6BJ2

HLA-B*35:01 presenting "IPLTEEAEL" to Alpha/Beta T cell receptor at 3.35Å 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. Class I alpha
HLA-B*35:01
['A']
3. Peptide
IPLTEEAEL
['C']
4. T cell receptor alpha
TRAV19
['D']
5. T cell receptor beta
TRBV5
['E']

Species


Locus / Allele group


Publication

Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding.

Sibener LV, Fernandes RA, Kolawole EM, Carbone CB, Liu F, McAffee D, Birnbaum ME, Yang X, Su LF, Yu W, Dong S, Gee MH, Jude KM, Davis MM, Groves JT, Goddard WA, Heath JR, Evavold BD, Vale RD, Garcia KC
Cell (2018) 174, 672-687.e27 [doi:10.1016/j.cell.2018.06.017]  [pubmed:30053426

TCR-signaling strength generally correlates with peptide-MHC binding affinity; however, exceptions exist. We find high-affinity, yet non-stimulatory, interactions occur with high frequency in the human T cell repertoire. Here, we studied human TCRs that are refractory to activation by pMHC ligands despite robust binding. Analysis of 3D affinity, 2D dwell time, and crystal structures of stimulatory versus non-stimulatory TCR-pMHC interactions failed to account for their different signaling outcomes. Using yeast pMHC display, we identified peptide agonists of a formerly non-responsive TCR. Single-molecule force measurements demonstrated the emergence of catch bonds in the activating TCR-pMHC interactions, correlating with exclusion of CD45 from the TCR-APC contact site. Molecular dynamics simulations of TCR-pMHC disengagement distinguished agonist from non-agonist ligands based on the acquisition of catch bonds within the TCR-pMHC interface. The isolation of catch bonds as a parameter mediating the coupling of TCR binding and signaling has important implications for TCR and antigen engineering for immunotherapy.

Structure deposition and release

Deposited: 2017-11-03
Released: 2018-07-25
Revised: 2020-07-29

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: IPLTEEAEL

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 ILE

TRP167
ARG62
TYR59
LEU163
TYR7
ASN63
TYR171
MET5
TYR159
P2 PRO

ASN63
TYR7
TYR159
PHE67
TYR9
ILE66
TYR99
P3 LEU

TYR9
ILE66
TYR99
LEU156
GLN155
ARG97
TYR159
ASN70
P4 THR

LEU163
GLN155
ARG62
ILE66
ASN70
P5 GLU

GLN155
P6 GLU

GLN155
TYR74
ARG97
ASN70
THR73
TYR9
TYR99
P7 ALA

SER77
THR73
TYR74
VAL152
TRP147
P8 GLU

GLU76
THR143
ASN80
THR73
TRP147
SER77
LYS146
P9 LEU

LYS146
TYR84
TYR123
ILE95
THR143
ASN80
TRP147
LEU81
SER77

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
LEU163
TRP167
TYR171
MET5
TYR59
ASN63
ILE66
TYR7
B Pocket

ALA24
VAL34
THR45
ASN63
ILE66
PHE67
TYR7
ASN70
TYR9
TYR99
C Pocket

ASN70
THR73
TYR74
TYR9
ARG97
D Pocket

ASP114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

ASP114
TRP147
VAL152
LEU156
ARG97
F Pocket

SER116
TYR123
THR143
LYS146
TRP147
SER77
ASN80
LEU81
TYR84
ILE95

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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-B*35:01
IPD-IMGT/HLA
[ipd-imgt:HLA34423]
        10        20        30        40        50        60
GSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DRNTQIFKTNTQTYRESLRNLRGYYNQSEAGSHIIQRMYGCDLGPDGRLLRGHDQSAYDG
       130       140       150       160       170       180
KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RADPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide
IPLTEEAEL

4. T cell receptor alpha
T cell receptor alpha
TRAV19
        10        20        30        40        50        60
QKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLFWYKQPPSGELVFLIRRNSFDEQNEIS
        70        80        90       100       110       120
GRYSWNFQKSTSSFNFTITASQVVDSAVYFCALSHNSGGSNYKLTFGKGTLLTVNPNIQN
       130       140       150       160       170       180
PDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVA
       190       200
WSNKSDFACANAFNNSIIPEDTFFPS

5. T cell receptor beta
T cell receptor beta
TRBV5
        10        20        30        40        50        60
AGVTQSPTHLIKTRGQQVTLRCSSQSGHNTVSWYQQALGQGPQFIFQYYREEENGRGNFP
        70        80        90       100       110       120
PRFSGLQFPNYSSELNVNALELDDSALYLCASSFRGGKTQYFGPGTRLLVLEDLKNVFPP
       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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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. 6BJ2 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 6BJ2 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 6BJ2 assembly 1  
Peptide only [cif]
  1. 6BJ2 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/6bj2

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