6ZKX

HLA-E*01:03 presenting "RLPAKAPLLGCG" to Alpha/Beta T cell receptor at 2.17Å 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

['B']

2. Class I alpha
HLA-E*01:03

['A']

3. Peptide
RLPAKAPLLGCG

['C']

4. T cell receptor alpha
TRAV21

['D']

5. T cell receptor beta
TRBV6

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

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: 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: Dodecamer (12 amino acids)

Sequence: RLPAKAPLLGCG

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

TRP167

LEU5

TYR159

ARG62

TYR59

GLU63

PHE33

TYR7

THR163

GLU58

TYR171

P10 GLY

THR80

CYS84

TYR123

ALA139

ILE142

ALA140

SER143

GLN141

P11 CYS

ALA139

GLN141

THR80

CYS84

GLN145

GLU144

TYR123

P12 GLY

ALA139

ALA140

GLN141

P2 LEU

HIS9

TYR7

SER24

SER66

ALA67

HIS99

TYR159

GLU63

MET45

P3 PRO

HIS99

GLN156

TYR159

TRP97

SER66

THR70

P4 ALA

SER66

ASP69

ARG62

P5 LYS

HIS155

GLN156

TRP97

P6 ALA

THR70

GLU152

TRP97

GLN156

PHE74

ILE73

P7 PRO

ASN77

GLU114

GLU152

GLN156

PHE74

ILE73

TRP97

ILE142

TRP133

PHE116

P8 LEU

GLN141

VAL76

GLU152

SER143

LYS146

SER147

ILE73

ILE142

ASN77

P9 LEU

ILE142

GLN141

PHE116

ASN77

SER143

LEU95

THR80

LEU124

TYR123

LEU81

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

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-E01:03 IPD-IMGT/HLA* [ipd-imgt:HLA34202]	10 20 30 40 50 60 MGSHSLKYFHTSVSRPGRGEPRFISVGYVDDTQFVRFDNDAASPRMVPRAPWMEQEGSEY 70 80 90 100 110 120 WDRETRSARDTAQIFRVNLRTLRGCYNQSEAGSHTLQWMHGCELGPDGRFLRGYEQFAYD 130 140 150 160 170 180 GKDYLTLNEDLRSWTAVDTAAQISEQKSNDASEAEHQRAYLEDTCVEWLHKYLEKGKETL 190 200 210 220 230 240 LHLEPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQQDGEGHTQDTELVETRPAGDG 250 260 270 TFQKWAAVVVPSGEEQRYTCHVQHEGLPEPVTLRWKP

3. Peptide	RLPAKAPLLGCG

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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Complete structures

Aligned structures [cif]

6ZKX assembly 1

Components

MHC Class I alpha chain [cif]

6ZKX assembly 1

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

6ZKX assembly 1

Peptide only [cif]

6ZKX assembly 1

Derived data

Data for this page [json]

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

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.