6AVG

HLA-B*07:02 presenting "APRGPHGGAASGL" 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

['H', 'A']

2. Class I alpha
HLA-B*07:02

['G', 'F']

3. Peptide
APRGPHGGAASGL

['Q', 'P']

4. T cell receptor alpha
TRAV4

['C']

5. T cell receptor beta
TRBV9

['D']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*07

Publication

Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide.

Chan KF, Gully BS, Gras S, Beringer DX, Kjer-Nielsen L, Cebon J, McCluskey J, Chen W, Rossjohn J

Nat Commun (2018) 9, 1026 [doi:10.1038/s41467-018-03321-w] [pubmed:29531227]

Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (>10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4+TRAJ21+-TRBV28+TRBJ2-3+ and TRAV4 + TRAJ8+-TRBV9+TRBJ2-1+), originating from a polyclonal T-cell repertoire, bind to HLA-B*07:02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-160-72. Comparison of the structures reveals that the two TCRs differentially binds NY-ESO-160-72-HLA-B*07:02 complex, and induces differing extent of conformational change of the NY-ESO-160-72 epitope. Accordingly, polyclonal TCR usage towards an extended HLA-I restricted tumour epitope translates to differing TCR recognition modes, whereby extensive flexibility at the TCR-pHLA-I interface engenders recognition.

Structure deposition and release

Deposited: 2017-09-02

Released: 2018-02-28

Revised: 2018-03-28

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Tridecamer (13 amino acids)

Sequence: APRGPHGGAASGL

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 ALA

TYR171

TYR159

TYR59

ASN63

MET5

ARG62

TRP167

TYR7

P10 ALA

THR73

GLU152

P11 SER

TRP147

LYS146

GLU152

ARG156

THR73

P12 GLY

TRP147

LYS146

SER77

THR73

P13 LEU

TYR123

LEU95

ASN80

TRP147

TYR84

LEU81

LYS146

SER77

TYR116

THR143

P2 PRO

TYR99

ARG62

TYR7

TYR67

TYR159

TYR9

ILE66

GLU45

ASN63

P3 ARG

ILE66

TYR99

GLN155

TYR116

ASP114

ARG156

GLN70

ARG62

TYR159

TYR9

P4 GLY

ARG62

ILE66

P5 PRO

GLN155

ILE66

P6 HIS

TYR159

ALA158

GLN155

GLU163

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

PRO67

ARG7

GLU70

VAL9

ARG99

C Pocket

GLU70

ALA73

PRO74

VAL9

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

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 LSLSGLEAIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHS 70 80 90 100 DLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-B07:02 IPD-IMGT/HLA* [ipd-imgt:HLA34746]	10 20 30 40 50 60 MLVMAPRTVLLLLSAALALTETWAGSHSMRYFYTSVSRPGRGEPRFISVGYVDDTQFVRF 70 80 90 100 110 120 DSDAASPREEPRAPWIEQEGPEYWDRNTQIYKAQAQTDRESLRNLRGYYNQSEAGSHTLQ 130 140 150 160 170 180 SMYGCDVGPDGRLLRGHDQYAYDGKDYIALNEDLRSWTAADTAAQITQRKWEAAREAEQR 190 200 210 220 230 240 RAYLEGECVEWLRRYLENGKDKLERADPPKTHVTHHPISDHEATLRCWALGFYPAEITLT 250 260 270 280 290 300 WQRDGEDQTQDTELVETRPAGDRTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP 310 320 330 340 350 360 SSQSTVPIVGIVAGLAVLAVVVIGAVVAAVMCRRKSSGGKGGSYSQAACSDSAQGSDVSL TA

3. Peptide	APRGPHGGAASGL

4. T cell receptor alpha T cell receptor alpha TRAV4	10 20 30 40 50 60 MLAKTTQPISMDSYEGQEVNITCSHNNIATNDYITWYQQFPSQGPRFIIQGYKTKVTNEV 70 80 90 100 110 120 ASLFIPADRKSSTLSLPRVSLSDTAVYYCLVVDQKLVFGTGTRLLVSPNIQNPDPAVYQL 130 140 150 160 170 180 RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFA 190 200 CANAFNNSIIPEDTFFPSPESS

5. T cell receptor beta T cell receptor beta TRBV9	10 20 30 40 50 60 MDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQGLQFLIQYYNGEERAKGN 70 80 90 100 110 120 ILERFSAQQFPDLHSELNLSSLELGDSALYFCASSGGHTGSNEQFFGPGTRLTVLEDLKN 130 140 150 160 170 180 VFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKE 190 200 210 220 230 240 QPALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEA WGRAD

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]

6AVG assembly 1

Components

MHC Class I alpha chain [cif]

6AVG assembly 1

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

6AVG assembly 1

Peptide only [cif]

6AVG assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/6avg

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.