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6ZKW

HLA-E*01:03 presenting "RLPAKAPLL" to Alpha/Beta T cell receptor at 2.26Å 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-E*01:03
['A']
3. Peptide
RLPAKAPLL
['C']
4. T cell receptor alpha
TRAV21
['D']
5. T cell receptor beta
TRBV6
['E']

Species


Locus / Allele group


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: 2020-06-30
Released: 2022-01-26
Revised: 2022-04-20

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: RLPAKAPLL

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 ARG

GLU63
LEU5
TRP167
TYR171
PHE33
TYR59
TYR7
ARG62
TYR159
THR163
P2 LEU

ARG62
SER24
HIS99
TYR159
GLU63
THR70
TYR7
MET45
SER66
ALA67
HIS9
P3 PRO

GLN156
ARG62
TRP97
TYR159
SER66
HIS99
THR70
P4 ALA

ARG62
SER66
ASP69
P5 LYS

HIS155
GLN156
TRP97
P6 ALA

GLU152
THR70
PHE74
GLN156
TRP97
ILE73
P7 PRO

SER147
GLU114
ASN77
GLU152
GLN156
ILE73
TRP133
PHE116
TRP97
P8 LEU

ASN77
SER143
GLU152
LYS146
ILE73
VAL76
SER147
P9 LEU

LEU124
PHE116
ILE142
LEU81
THR80
ASN77
TYR84
SER143
TYR123
LEU95
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
LEU5
TYR59
GLU63
SER66
TYR7
B Pocket

SER24
VAL34
MET45
GLU63
SER66
ALA67
TYR7
THR70
HIS9
HIS99
C Pocket

THR70
ILE73
PHE74
HIS9
TRP97
D Pocket

GLU114
HIS155
GLN156
TYR159
LEU160
HIS99
E Pocket

GLU114
SER147
GLU152
GLN156
TRP97
F Pocket

PHE116
TYR123
SER143
LYS146
SER147
ASN77
THR80
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. Class I alpha
HLA-E*01:03
IPD-IMGT/HLA
[ipd-imgt:HLA34202]
        10        20        30        40        50        60
GSHSLKYFHTSVSRPGRGEPRFISVGYVDDTQFVRFDNDAASPRMVPRAPWMEQEGSEYW
        70        80        90       100       110       120
DRETRSARDTAQIFRVNLRTLRGYYNQSEAGSHTLQWMHGCELGPDGRFLRGYEQFAYDG
       130       140       150       160       170       180
KDYLTLNEDLRSWTAVDTAAQISEQKSNDASEAEHQRAYLEDTCVEWLHKYLEKGKETLL
       190       200       210       220       230       240
HLEPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQQDGEGHTQDTELVETRPAGDGT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPEPVTLRWKP

3. Peptide
RLPAKAPLL

4. T cell receptor alpha
T cell receptor alpha
TRAV21
        10        20        30        40        50        60
MAQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFRQDPGKGLTSLLLIQSSQREQTS
        70        80        90       100       110       120
GRLNASLDKSSGRSTLYIAASQPGDSATYLCAVTNQAGTALIFGKGTTLSVSSNIQNPDP
       130       140       150       160       170       180
AVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSN
       190
KSDFACANAFNNSIIPEDT

5. T cell receptor beta
T cell receptor beta
TRBV6
        10        20        30        40        50        60
NAGVTQTPKFQVLKTGQSMTLQCSQDMNHEYMSWYRQDPGMGLRLIHYSVGAGITDQGEV
        70        80        90       100       110       120
PNGYNVSRSTTEDFPLRLLSAAPSQTSVYFCASSYSIRGSRGEQFFGPGTRLTVLEDLKN
       130       140       150       160       170       180
VFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKE
       190       200       210       220       230       240
QPALNDSRYALSSRLRVSATFWQDPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEA

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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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. 6ZKW assembly 1  

Components

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

Derived data

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

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