7JWI

H2-Db presenting "ASNENMETM" to Alpha/Beta T cell receptor at 3.02Å 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
H2-Db

['A']

3. Peptide
ASNENMETM

['C']

4. T cell receptor alpha
TRAV14

['D']

5. T cell receptor beta
TRBV17

['E']

Information on this structure on STCRdab.

Species

Mus musculus (Mouse)

Locus / Allele group

H2-D / H2-Db

Publication

Canonical T cell receptor docking on peptide-MHC is essential for T cell signaling.

Zareie P, Szeto C, Farenc C, Gunasinghe SD, Kolawole EM, Nguyen A, Blyth C, Sng XYX, Li J, Jones CM, Fulcher AJ, Jacobs JR, Wei Q, Wojciech L, Petersen J, Gascoigne NRJ, Evavold BD, Gaus K, Gras S, Rossjohn J, La Gruta NL

Science (2021) 372, [doi:10.1126/science.abe9124] [pubmed:34083463]

T cell receptor (TCR) recognition of peptide-major histocompatibility complexes (pMHCs) is characterized by a highly conserved docking polarity. Whether this polarity is driven by recognition or signaling constraints remains unclear. Using "reversed-docking" TCRβ-variable (TRBV) 17+ TCRs from the naïve mouse CD8+ T cell repertoire that recognizes the H-2Db-NP366 epitope, we demonstrate that their inability to support T cell activation and in vivo recruitment is a direct consequence of reversed docking polarity and not TCR-pMHCI binding or clustering characteristics. Canonical TCR-pMHCI docking optimally localizes CD8/Lck to the CD3 complex, which is prevented by reversed TCR-pMHCI polarity. The requirement for canonical docking was circumvented by dissociating Lck from CD8. Thus, the consensus TCR-pMHC docking topology is mandated by T cell signaling constraints.

Structure deposition and release

Deposited: 2020-08-25

Released: 2021-07-07

Revised: 2021-07-07

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: ASNENMETM

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 ALA

TYR59

LYS66

GLU163

TYR7

GLU63

PHE33

MET5

TYR171

TYR159

TRP167

P2 SER

TYR159

TYR7

LYS66

TYR45

GLU163

GLU63

P3 ASN

GLN70

TYR156

HIS155

TYR159

GLU9

LYS66

P4 GLU

GLY69

TYR156

LYS66

GLN65

GLN70

P5 ASN

TYR156

TRP73

PHE74

PHE116

GLN97

GLU9

GLN70

P6 MET

TRP73

ALA152

TYR156

HIS155

P7 GLU

TRP73

TRP147

SER150

LYS146

P8 THR

THR143

ASN80

TRP147

SER77

LYS146

VAL76

TRP73

P9 MET

TYR123

LYS146

PHE116

THR143

LEU81

SER77

ASN80

ILE124

TRP147

LEU95

ILE142

TYR84

TRP73

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

ALA163

THR167

TRP171

ALA5

ARG59

ASP63

ASN66

ARG7

B Pocket

ALA24

THR34

ARG45

ASP63

ASN66

PRO67

ARG7

GLU70

LEU9

ARG99

C Pocket

GLU70

ALA73

PRO74

LEU9

TRP97

D Pocket

GLY114

LYS155

THR156

ALA159

ALA160

ARG99

E Pocket

GLY114

TYR147

GLU152

THR156

TRP97

F Pocket

SER116

SER123

GLU143

ASP146

TYR147

GLU77

GLY80

PRO81

TRP84

GLU95

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 H2-Db	10 20 30 40 50 60 MGAMAPRTLLLLLAAALAPTQTRAGPHSMRYFETAVSRPGLEEPRYISVGYVDNKEFVRF 70 80 90 100 110 120 DSDAENPRYEPRAPWMEQEGPEYWERETQKAKGQEQWFRVSLRNLLGYYNQSAGGSHTLQ 130 140 150 160 170 180 QMSGCDLGSDWRLLRGYLQFAYEGRDYIALNEDLKTWTAADMAAQITRRKWEQSGAAEHY 190 200 210 220 230 240 KAYLEGECVEWLHRYLKNGNATLLRTDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLT 250 260 270 280 290 300 WQLNGEELTQDMELVETRPAGDGTFQKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWEP 310 320 330 340 350 360 PPSTDSYMVIVAVLGVLGAMAIIGAVVAFVMKRRRNTGGKGGDYALAPGSQSSEMSLRDC KA

3. Peptide	ASNENMETM

4. T cell receptor alpha T cell receptor alpha TRAV14	10 20 30 40 50 60 QQQVRQSPQSLTVWEGETAILNCSYEDSTFNYFPWYQQFPGEGPALLISIRSVSDKKEDG 70 80 90 100 110 120 RFTIFFNKREKKLSLHITDSQPGDSATYFCAASETSGSWQLIFGSGTTVSVSPNIQNPDP 130 140 150 160 170 180 AVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSN 190 200 KSDFACANAFNNSIIPEDTFFPSPESS

5. T cell receptor beta T cell receptor beta TRBV17	10 20 30 40 50 60 DTTVKQNPRYKLARVGKPVNLICSQTMNHDTMYWYQKKPNQAPKLLLFYYDKILNREADT 70 80 90 100 110 120 FEKFQSSRPNNSFCSLYIGSAGLEYSAMYLCASSRDLGRDTQYFGPGTRLTVLEDLKNVF 130 140 150 160 170 180 PPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQP 190 200 210 220 230 240 ALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWG RAD

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]

7JWI assembly 1

Components

MHC Class I alpha chain [cif]

7JWI assembly 1

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

7JWI assembly 1

Peptide only [cif]

7JWI assembly 1

Derived data

Data for this page [json]

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

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.