7DZM

HLA-B*81:01 presenting "TPQDLNTML" to Alpha/Beta T cell receptor at 2.25Å 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*81:01

['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*81

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

PHE35

TRP169

TYR61

ARG64

TYR173

TYR161

GLU165

ASN65

TYR9

MET7

P2 PRO

TYR9

TYR161

ASN65

TYR101

TYR11

ILE68

GLU47

TYR69

P3 GLN

TYR161

GLN72

TYR11

ASN116

LEU158

TYR101

TYR118

ILE68

P4 ASP

ILE68

TYR161

P5 LEU

GLN72

GLN157

LEU158

ILE68

TYR161

P6 ASN

ALA71

GLN72

THR75

P7 THR

ASP76

TYR118

THR75

SER79

VAL154

GLN72

LEU149

P8 MET

SER79

GLU78

ASN82

LEU149

THR75

LYS148

P9 LEU

SER145

TYR86

LEU149

SER79

ILE126

LYS148

TYR118

TYR125

LEU83

ASN82

LEU97

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

GLY163

GLU167

ARG171

SER5

GLU59

ARG63

GLN66

ARG7

B Pocket

ILE24

PHE34

ARG45

ARG63

GLN66

ILE67

ARG7

ALA70

PHE9

MET99

C Pocket

ALA70

GLN73

THR74

PHE9

GLN97

D Pocket

HIS114

GLU155

GLN156

ALA159

TYR160

MET99

E Pocket

HIS114

LYS147

ARG152

GLN156

GLN97

F Pocket

GLN116

ASP123

ILE143

ARG146

LYS147

GLU77

ARG80

ASN81

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-B81:01 IPD-IMGT/HLA* [ipd-imgt:HLA24269]	10 20 30 40 50 60 GGSHSMRYFYTSVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPREEPRAPWIEQEGPEY 70 80 90 100 110 120 WDRNTQIYKAQAQTDRESLRNLRGYYNQSEAGSHTLQSMYGCDVGPDGRLLRGHNQYAYD 130 140 150 160 170 180 GKDYIALNEDLRSWTAADTAAQISQRKLEAARVAEQLRAYLEGECVEWLRRYLENGKDKL 190 200 210 220 230 240 ERADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDR 250 260 270 TFQKWTAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEPS

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 NKSDFACANAFNNSIIPEDTFFPSPEL

5. T cell receptor beta T cell receptor beta TRBV12	10 20 30 40 50 60 AGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRQTMMRGLELLIYFNNNVPIDDSGMP 70 80 90 100 110 120 EDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSLGIDAIYFGEGSWLTVVEDLKNVFPP 130 140 150 160 170 180 EVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPAL 190 200 210 220 230 240 NDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRA D

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]

7DZM assembly 1

Components

MHC Class I alpha chain [cif]

7DZM assembly 1

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

7DZM assembly 1

Peptide only [cif]

7DZM assembly 1

Derived data

Data for this page [json]

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

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.