7PHR

HLA-A*02:01 presenting "YLEPGPVTV" to Alpha/Beta T cell receptor at 3.08Å 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

['L']

2. Class I alpha
HLA-A*02:01

['H']

3. Peptide
YLEPGPVTV

['P']

4. T cell receptor alpha
TRAV17

['A']

5. T cell receptor beta
TRBV19

['B']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-A / HLA-A*02

Publication

Structure of a fully assembled tumor-specific T cell receptor ligated by pMHC.

Sušac L, Vuong MT, Thomas C, von Bülow S, O'Brien-Ball C, Santos AM, Fernandes RA, Hummer G, Tampé R, Davis SJ

Cell (2022) 185, 3201-3213.e19 [doi:10.1016/j.cell.2022.07.010] [pubmed:35985289]

The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the receptor binds to peptide-loaded major histocompatibility complex (pMHC) molecules, we used cryogenic electron microscopy to determine the structure of a tumor-reactive TCRαβ/CD3δγε₂ζ₂ complex bound to a melanoma-specific human class I pMHC at 3.08 Å resolution. The antigen-bound complex comprises 11 subunits stabilized by multivalent interactions across three structural layers, with clustered membrane-proximal cystines stabilizing the CD3-εδ and CD3-εγ heterodimers. Extra density sandwiched between transmembrane helices reveals the involvement of sterol lipids in TCR assembly. The geometry of the pMHC/TCR complex suggests that efficient TCR scanning of pMHC requires accurate pre-positioning of T cell and antigen-presenting cell membranes. Comparisons of the ligand-bound and unliganded receptors, along with molecular dynamics simulations, indicate that TCRs can be triggered in the absence of spontaneous structural rearrangements.

Structure deposition and release

Deposited: 2021-08-18

Released: 2022-08-31

Revised: 2022-08-31

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: YLEPGPVTV

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 TYR

THR163

TRP167

TYR159

TYR59

TYR7

PHE33

MET5

TYR99

GLU63

LYS66

TYR171

P2 LEU

MET45

TYR99

GLU63

LYS66

VAL67

TYR159

TYR7

HIS70

PHE9

P3 GLU

HIS70

LEU156

GLN155

TYR99

LYS66

TYR159

P4 PRO

LYS66

GLN155

HIS70

ALA69

P5 GLY

HIS70

ALA69

P6 PRO

ARG97

THR73

HIS70

ALA69

P7 VAL

ALA150

LYS146

VAL152

ARG97

THR73

ASP77

TRP147

P8 THR

LYS146

ASP77

THR73

VAL76

TRP147

P9 VAL

TYR123

LYS146

ASP77

THR80

TYR84

TRP147

THR143

LEU81

THR142

TYR116

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

TRP159

HIS163

GLN167

TYR171

HIS5

PRO59

TRP63

GLN66

HIS7

B Pocket

VAL24

PHE34

PHE45

TRP63

GLN66

GLU67

HIS7

GLU70

HIS9

GLN99

C Pocket

GLU70

ASP73

GLY74

HIS9

TYR97

D Pocket

ASP114

THR155

LYS156

TRP159

GLU160

GLN99

E Pocket

ASP114

ALA147

ALA152

LYS156

TYR97

F Pocket

GLY116

ARG123

ARG143

THR146

ALA147

ARG77

LYS80

ALA81

GLN84

GLY95

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 MGIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSK 70 80 90 100 DWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-A02:01 IPD-IMGT/HLA* [ipd-imgt:HLA35266]	10 20 30 40 50 60 MGSSHHHHHHGSGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPR 70 80 90 100 110 120 APWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWR 130 140 150 160 170 180 FLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWL 190 200 210 220 230 240 RRYLENGKETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDT 250 260 270 280 290 300 ELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEPSSQPEDQVDPRL IDGK

3. Peptide	YLEPGPVTV

4. T cell receptor alpha T cell receptor alpha TRAV17	10 20 30 40 50 60 MSQQGEEDPQALSIQEGENATMNCSYKTSINNLQWYRQNSGRGLVHLILIRSNEREKHSG 70 80 90 100 110 120 RLRVTLDTSKKSSSLLITASRAADTASYFCATDGSTPMQFGKGTRLSVIPNIQNPDPAVY 130 140 150 160 170 180 QLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSD 190 200 210 220 230 240 FACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGF 250 NLLMTLRLWSS

5. T cell receptor beta T cell receptor beta TRBV19	10 20 30 40 50 60 MDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSWAQGDFQKGD 70 80 90 100 110 120 IAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASSWGAPYEQYFGPGTRLTVTEDLNKVF 130 140 150 160 170 180 PPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQP 190 200 210 220 230 240 ALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWG 250 260 270 280 RADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF

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]

7PHR assembly 1

Components

MHC Class I alpha chain [cif]

7PHR assembly 1

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

7PHR assembly 1

Peptide only [cif]

7PHR assembly 1

Derived data

Data for this page [json]

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

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.