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7NDT

HLA-E*01:03 presenting "VMAPRTLIL" 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
['BBB', 'GGG']
2. Class I alpha
HLA-E*01:03
['AAA', 'FFF']
4. Peptide
VMAPRTLIL
['CCC', 'HHH']
5. T cell receptor alpha
['DDD', 'III']
6. T cell receptor beta
['EEE', 'JJJ']

Species

Locus / Allele group

HLA-E / HLA-E*01

Publication

Structure-guided stabilization of pathogen-derived peptide-HLA-E complexes using non-natural amino acids conserves native TCR recognition.

Barber C, De Souza VA, Paterson RL, Martin-Urdiroz M, Mulakkal NC, Srikannathasan V, Connolly M, Phillips G, Foong-Leong T, Pengelly R, Karuppiah V, Grant T, Dembek M, Verma A, Gibbs-Howe D, Blicher TH, Knox A, Robinson RA, Cole DK, Leonard S
Eur J Immunol (2022) 52, 618-632 [doi:10.1002/eji.202149745]  [pubmed:35108401] 

The nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs.

Structure deposition and release

Deposited: 2021-02-02
Released: 2022-01-26
Revised: 2022-07-27

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: VMAPRTLIL

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.

Binding cleft pockets


Peptide sidechain binding pockets (static)
Peptide terminii and backbone binding residues (static)
A Pocket

ALA159
ASP163
GLU167
LYS171
SER5
GLU59
ARG63
ARG66
LYS7
B Pocket

ILE24
PHE34
ARG45
ARG63
ARG66
SER67
LYS7
ASP70
PHE9
MET99
C Pocket

ASP70
GLN73
ILE74
PHE9
GLN97
D Pocket

TYR114
GLU155
HIS156
ALA159
TYR160
MET99
E Pocket

TYR114
LYS147
SER152
HIS156
GLN97
F Pocket

GLN116
ASP123
ILE143
GLN146
LYS147
VAL77
ARG80
THR81
GLY84
THR95

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-E*01:03
IPD-IMGT/HLA
[ipd-imgt:HLA34202]
        10        20        30        40        50        60
MGSHSLKYFHTSVSRPGRGEPRFISVGYVDDTQFVRFDNDAASPRMVPRAPWMEQEGSEY
        70        80        90       100       110       120
WDRETRSARDTAQIFRVNLRTLRGYYNQSEAGSHTLQWMHGCELGPDGRFLRGYEQCAYD
       130       140       150       160       170       180
GKDYLTLNEDLRSWTAVDTAAQISEQKSNDASEAEHQRAYLEDTCVEWLHKYLEKGKETL
       190       200       210       220       230       240
LHLEPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQQDGEGHTQDTELVETRPAGDG
       250       260       270
TFQKWAAVVVPSGEEQRYTCHVQHEGLPEPVTLRWKP
4. Peptide
VMAPRTLIL
5. T cell receptor alpha
T cell receptor alpha
        10        20        30        40        50        60
MAAKTTQPPSMDVAEGRAANLPCNHSTISGNEYVYWYRQIHSQGPQYIIHGLKNNETNEM
        70        80        90       100       110       120
ASLIITEDRKSSTLILPHATLRDTAVYYCIVVRSSNTGKLIFGQGTTLQVKPDIQNPDPA
       130       140       150       160       170       180
VYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNK
       190
SDFACANAFNNSIIPEDT
6. T cell receptor beta
T cell receptor beta
        10        20        30        40        50        60
MEAGVTQFPSHSVIEKGQTVTLRCDPISGHDNLYWYRRVMGKEIKFLLHFVKESKQDESG
        70        80        90       100       110       120
MPNNRFLAERTGGTYSTLKVQPAELEDSGVYFCASSQDRDTQYFGPGTRLTVLEDLKNVF
       130       140       150       160       170       180
PPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQP
       190       200       210       220       230       240
ALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWG

RAD

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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   e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif
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. 7NDT assembly 1  

Components

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

Derived data

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

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.