2NX5

HLA-B*35:01 presenting "EPLPQGQLTAY" to Alpha/Beta T cell receptor at 2.70Å 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', 'G', 'L', 'R']

2. Class I alpha
HLA-B*35:01

['A', 'F', 'K', 'Q']

3. Peptide
EPLPQGQLTAY

['C', 'H', 'M', 'S']

4. T cell receptor alpha
TRAV1

['D']

5. T cell receptor beta
TRBV10

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*35

Publication

A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule.

Tynan FE, Reid HH, Kjer-Nielsen L, Miles JJ, Wilce MC, Kostenko L, Borg NA, Williamson NA, Beddoe T, Purcell AW, Burrows SR, McCluskey J, Rossjohn J

Nat. Immunol. (2007) 8, 268-76 [doi:10.1038/ni1432] [pubmed:17259989]

Plasticity of the T cell receptor (TCR) is a hallmark of major histocompatibility complex (MHC)-restricted T cell recognition. However, it is unclear whether interactions of TCR and peptide-MHC class I (pMHCI) always conform to this paradigm. Here we describe the structure of a TCR, ELS4, in its non-ligand-bound form and in complex with a prominent 'bulged' Epstein-Barr virus peptide bound to HLA-B(*)3501. This complex was atypical of previously characterized TCR-pMHCI interactions in that a rigid face of the TCR crumpled the bulged antigenic determinant. This peptide 'bulldozing' created a more featureless pMHCI determinant, allowing the TCR to maximize MHC class I contacts essential for MHC class I restriction of TCR recognition. Our findings represent a mechanism of antigen recognition whereby the plasticity of the T cell response is dictated mainly by adjustments in the MHC-bound peptide.

Structure deposition and release

Deposited: 2006-11-16

Released: 2007-02-27

Revised: 2011-07-13

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Undecamer (11 amino acids)

Sequence: EPLPQGQLTAY

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 GLU

TYR159

TYR7

ASN63

MET5

ARG62

TYR171

TRP167

TYR59

PHE33

P10 ALA

ASN80

THR73

LYS146

TRP147

GLU76

SER77

THR143

P11 TYR

ILE124

TYR74

GLN96

TYR84

LEU81

ILE142

SER77

THR143

ASN80

SER116

LYS146

TRP147

ARG97

TYR123

ILE95

P2 PRO

TYR99

TYR159

ASN63

TYR7

PHE67

TYR9

ILE66

P3 LEU

ARG97

TYR99

TYR9

GLN155

ILE66

LEU156

TYR159

ASN70

P4 PRO

GLN155

ILE66

LEU163

TYR159

P5 GLN

TYR9

GLN155

ASN70

TYR74

ARG97

P6 GLY

THR69

THR73

ASN70

P7 GLN

THR73

P8 LEU

LYS146

VAL152

TRP147

ALA150

P9 THR

SER77

THR73

VAL152

TRP147

ARG97

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

TYR159

LEU163

TRP167

TYR171

MET5

TYR59

ASN63

ILE66

TYR7

B Pocket

ALA24

VAL34

THR45

ASN63

ILE66

PHE67

TYR7

ASN70

TYR9

TYR99

C Pocket

ASN70

THR73

TYR74

TYR9

ARG97

D Pocket

ASP114

GLN155

LEU156

TYR159

LEU160

TYR99

E Pocket

ASP114

TRP147

VAL152

LEU156

ARG97

F Pocket

SER116

TYR123

THR143

LYS146

TRP147

SER77

ASN80

LEU81

TYR84

ILE95

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 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW 70 80 90 SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-B35:01 IPD-IMGT/HLA* [ipd-imgt:HLA34423]	10 20 30 40 50 60 GSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRNTQIFKTNTQTYRESLRNLRGYYNQSEAGSHIIQRMYGCDLGPDGRLLRGHDQSAYDG 130 140 150 160 170 180 KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQ 190 200 210 220 230 240 RADPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide	EPLPQGQLTAY

4. T cell receptor alpha T cell receptor alpha TRAV1	10 20 30 40 50 60 QNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQHAGEAPTFLSYNVLDGLEEKGRFS 70 80 90 100 110 120 SFLSRSKGYSYLLLKELQMKDSASYLCAVQASGGSYIPTFGRGTSLIVHPYIQNPDPAVY 130 140 150 160 170 180 QLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSD FACANAFN

5. T cell receptor beta T cell receptor beta TRBV10	10 20 30 40 50 60 DAGITQSPRHKVTETGTPVTLRCHQTENHRYMYWYRQDPGHGLRLIHYSYGVKDTDKGEV 70 80 90 100 110 120 SDGYSVSRSKTEDFLLTLESATSSQTSVYFCATGTGDSNQPQHFGDGTRLSILEDLNKVF 130 140 150 160 170 180 PPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQP 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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Please take note of the data license. Using data from this site assumes that you have read and will comply with the license.

Complete structures

Aligned structures [cif]

2NX5 assembly 1

Components

MHC Class I alpha chain [cif]

2NX5 assembly 1

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

2NX5 assembly 1

Peptide only [cif]

2NX5 assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/2nx5

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.