7DZN

HLA-B*42:01 presenting "TPQDLNTML" to Alpha/Beta T cell receptor at 2.63Å 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-B*42:01

['A']

3. Peptide
TPQDLNTML

['C']

4. T cell receptor alpha
TRAV26

['E']

5. T cell receptor beta
TRBV12

['D']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*42

Publication

Cross-reactive TCR with alloreactivity for immunodominant HIV-1 epitope Gag TL9 with enhanced control of viral infection

Liu, Y., San, D., Yin, L.

(2021) - [doi:10.1101/2021.06.06.447276]

ABSTRACT

Although both HLA B*81:01 and HLA B*42:01 are members of the B7 supertype and can present many of the same HIV-1 epitopes, the identification of a dual-reactive T-cell phenotype was unexpected, since structural data suggested that TL9 peptide binds to each allele in a distinct conformation. How the dual-reactive TCR recognizes these radically distinct p-MHC surfaces is revealed by our structural study, that the introduction of TCR T18A induces a molecular switch of the TL9 peptide in B4201 to approach its conformation in B8101. Most importantly, unique docking of CDR3β towards MHC but not peptide ligand strengthens the peptide tolerance of T18A, extends the ability of TCR to adapt mutations. Moreover, the high affinity of dual-reactive TCR for WT and escape mutant TL9 highlights the functional advantage of the alloreactive phenotype.

Structure deposition and release

Deposited: 2021-01-25

Released: 2022-01-26

Revised: 2022-01-26

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: TPQDLNTML

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 THR

TYR61

ARG64

THR165

ASN65

TRP169

MET7

PHE35

TYR173

TYR9

TYR161

P2 PRO

GLU47

ILE68

TYR101

TYR161

TYR69

ASN65

TYR11

TYR9

P3 GLN

ASP158

TYR11

TYR101

TYR161

TYR118

ILE68

ASN116

P4 ASP

TYR161

ILE68

ARG64

P5 LEU

ASP158

GLN157

GLN72

ILE68

P6 ASN

GLN72

THR75

ALA71

P7 THR

TYR118

GLN72

ASP76

THR75

VAL154

ASP158

SER79

TRP149

P8 MET

ASN82

LYS148

THR75

TRP149

SER79

GLU78

P9 LEU

TYR118

TYR125

LEU83

ASN82

LEU97

TYR86

SER79

LYS148

TRP149

THR145

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

ARG159

GLU163

VAL167

ARG171

HIS5

PRO59

ASP63

THR66

MET7

B Pocket

PHE24

GLN34

PRO45

ASP63

THR66

GLN67

MET7

LYS70

TYR9

SER99

C Pocket

LYS70

ALA73

GLN74

TYR9

LEU97

D Pocket

GLY114

ALA155

GLU156

ARG159

ALA160

SER99

E Pocket

GLY114

ARG147

ALA152

GLU156

LEU97

F Pocket

ASN116

LYS123

GLN143

GLN146

ARG147

ARG77

LEU80

ARG81

ARG84

HIS95

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-B42:01 IPD-IMGT/HLA* [ipd-imgt:HLA34781]	10 20 30 40 50 60 MGGSHSMRYFYTSVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPREEPRAPWIEQEGPE 70 80 90 100 110 120 YWDRNTQIYKAQAQTDRESLRNLRGYYNQSEAGSHTLQSMYGCDVGPDGRLLRGHNQYAY 130 140 150 160 170 180 DGKDYIALNEDLRSWTAADTAAQITQRKWEAARVAEQDRAYLEGTCVEWLRRYLENGKDT 190 200 210 220 230 240 LERADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGD 250 260 270 RTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEPS

3. Peptide	TPQDLNTML

4. T cell receptor alpha T cell receptor alpha TRAV26	10 20 30 40 50 60 MGDAKTTQPPSMDCAEGRAANLPCNHSTISGNEYVYWYRQIHSQGPQYIIHGLKNNETNE 70 80 90 100 110 120 MASLIITEDRKSSTLILPHATLRDTAVYYCIVRGLNNAGNMLTFGGGTRLMVKPDIQNPD 130 140 150 160 170 180 PAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWS 190 200 NKSDFACANAFNNSIIPEDTFFPS

5. T cell receptor beta T cell receptor beta TRBV12	10 20 30 40 50 60 MGDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRQTMMRGLELLIYFNNNVPIDDS 70 80 90 100 110 120 GMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSLGIDAIYFGEGSWLTVVEDLKNV 130 140 150 160 170 180 FPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQ 190 200 210 220 230 240 PALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAW 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]

7DZN assembly 1

Components

MHC Class I alpha chain [cif]

7DZN assembly 1

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

7DZN assembly 1

Peptide only [cif]

7DZN assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/7dzn

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.