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3HG1

HLA-A*02:01 presenting "ELAGIGILTV" to Alpha/Beta T cell receptor at 3.00Å 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-A*02:01
['A']
3. Peptide
ELAGIGILTV
['C']
4. T cell receptor alpha
TRAV12
['D']
5. T cell receptor beta
TRBV30
['E']

Species

Locus / Allele group

HLA-A / HLA-A*02

Publication

Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor.

Cole DK, Yuan F, Rizkallah PJ, Miles JJ, Gostick E, Price DA, Gao GF, Jakobsen BK, Sewell AK
J. Biol. Chem. (2009) 284, 27281-9 [doi:10.1074/jbc.M109.022509]  [pubmed:19605354] 

CD8(+) T-cells specific for MART-1-(26-35), a dominant melanoma epitope restricted by human leukocyte antigen (HLA)-A*0201, are exceptionally common in the naive T-cell repertoire. Remarkably, the TRAV12-2 gene is used to encode the T-cell receptor alpha (TCRalpha) chain in >87% of these T-cells. Here, the molecular basis for this genetic bias is revealed from the structural and thermodynamic properties of an archetypal TRAV12-2-encoded TCR complexed to the clinically relevant heteroclitic peptide, ELAGIGILTV, bound to HLA-A*0201 (A2-ELA). Unusually, the TRAV12-2 germ line-encoded regions of the TCR dominate the major atomic contacts with the peptide at the TCR/A2-ELA interface. This "innate" pattern of antigen recognition probably explains the unique characteristics and extraordinary frequencies of CD8(+) T-cell responses to this epitope.

Structure deposition and release

Deposited: 2009-05-13
Released: 2009-07-28
Revised: 2014-04-09

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: ELAGIGILTV

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 GLU

GLU63
TYR159
TYR59
TYR7
THR163
TRP167
LYS66
MET5
PHE33
TYR171
 P10 VAL

ARG97
THR80
TYR84
LEU81
THR142
ASP77
TRP147
THR143
LYS146
TYR123
TYR116
 P2 LEU

PHE9
MET45
VAL67
TYR99
GLU63
TYR159
TYR7
LYS66
HIS70
 P3 ALA

HIS70
TYR99
TYR159
LYS66
 P4 GLY

TYR159
LYS66
 P5 ILE

LEU156
GLN155
ALA158
TYR159
 P6 GLY

GLN155
VAL152
HIS114
LEU156
 P7 ILE

HIS114
LEU156
GLN155
ARG97
TYR99
THR73
VAL152
HIS70
 P8 LEU

TRP147
ARG97
THR73
VAL152
ALA150
ASP77
 P9 THR

TRP147
VAL76
THR80
THR73
ASP77
THR143
LYS146

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
THR163
TRP167
TYR171
MET5
TYR59
GLU63
LYS66
TYR7
B Pocket

ALA24
VAL34
MET45
GLU63
LYS66
VAL67
TYR7
HIS70
PHE9
TYR99
C Pocket

HIS70
THR73
HIS74
PHE9
ARG97
D Pocket

HIS114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

HIS114
TRP147
VAL152
LEU156
ARG97
F Pocket

TYR116
TYR123
THR143
LYS146
TRP147
ASP77
THR80
LEU81
TYR84
VAL95

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-A*02:01
IPD-IMGT/HLA
[ipd-imgt:HLA35266]
        10        20        30        40        50        60
GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG
       130       140       150       160       170       180
KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT
       250       260       270
FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEP
3. Peptide
ELAGIGILTV
4. T cell receptor alpha
T cell receptor alpha
TRAV12
        10        20        30        40        50        60
QEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMFIYSNGDKEDGRF
        70        80        90       100       110       120
TAQLNKASQYVSLLIRDSQPSDSATYLCAVNVAGKSTFGDGTTLTVKPNIQNPDPAVYQL
       130       140       150       160       170       180
RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFA
       190
CANAFNNSIIPEDT
5. T cell receptor beta
T cell receptor beta
TRBV30
        10        20        30        40        50        60
SQTIHQWPATLVQPVGSPLSLECTVEGTSNPNLYWYRQAAGRGLQLLFYSVGIGQISSEV
        70        80        90       100       110       120
PQNLSASRPQDRQFILSSKKLLLSDSGFYLCAWSETGLGTGELFFGEGSRLTVLEDLKNV
       130       140       150       160       170       180
FPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQ
       190       200       210       220       230       240
PALNDSRYALSSRLRVSATFWQDPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAW

GRAD

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]
  1. 3HG1 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 3HG1 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 3HG1 assembly 1  
Peptide only [cif]
  1. 3HG1 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/3hg1

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.