4NQX

HLA-A*01:01 binding "CTELKLNDY" at 2.00Å 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

1. Beta 2 microglobulin

['B', 'D', 'F', 'H', 'J', 'L']

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

['A', 'C', 'E', 'G', 'I', 'K']

3. Peptide
CTELKLNDY

['M', 'N', 'O', 'P', 'Q', 'R']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-A / HLA-A*01

Publication

Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities.

Quiñones-Parra S, Grant E, Loh L, Nguyen TH, Campbell KA, Tong SY, Miller A, Doherty PC, Vijaykrishna D, Rossjohn J, Gras S, Kedzierska K

Proc. Natl. Acad. Sci. U.S.A. (2014) 111, 1049-54 [doi:10.1073/pnas.1322229111] [pubmed:24395804]

The absence of preexisting neutralizing antibodies specific for the novel A (H7N9) influenza virus indicates a lack of prior human exposure. As influenza A virus-specific CD8(+) T lymphocytes (CTLs) can be broadly cross-reactive, we tested whether immunogenic peptides derived from H7N9 might be recognized by memory CTLs established following infection with other influenza strains. Probing across multiple ethnicities, we identified 32 conserved epitopes derived from the nucleoprotein (NP) and matrix-1 (M1) proteins. These NP and M1 peptides are presented by HLAs prevalent in 16-57% of individuals. Remarkably, some HLA alleles (A*0201, A*0301, B*5701, B*1801, and B*0801) elicit robust CTL responses against any human influenza A virus, including H7N9, whereas ethnicities where HLA-A*0101, A*6801, B*1501, and A*2402 are prominent, show limited CTL response profiles. By this criterion, some groups, especially the Alaskan and Australian Indigenous peoples, would be particularly vulnerable to H7N9 infection. This dissection of CTL-mediated immunity to H7N9 thus suggests strategies for both vaccine delivery and development.

Structure deposition and release

Deposited: 2013-11-26

Released: 2013-12-25

Revised: 2014-02-05

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: CTELKLNDY

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 CYS

TYR7

CYS164

TYR171

TYR59

ARG163

GLU63

GLY167

MET5

TYR159

P2 THR

MET45

TYR99

MET67

TYR159

PHE9

ASN66

HIS70

ARG163

GLU63

TYR7

P3 GLU

TYR159

ASN66

TYR99

ARG163

GLN155

HIS70

ARG156

P4 LEU

ALA69

HIS70

GLN62

ASN66

ARG163

P5 LYS

ALA69

ARG156

HIS70

P6 LEU

THR73

ASP74

ILE97

ARG114

HIS70

TYR99

ALA69

P7 ASN

THR73

ARG114

ALA152

TRP147

ARG156

ASN77

P8 ASP

LYS146

THR73

ALA76

THR143

THR80

TRP147

ASN77

P9 TYR

TYR123

LYS146

ILE97

ASP116

ILE124

THR143

LEU81

ASN77

THR80

TRP147

ILE95

ILE142

TYR84

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

ARG163

GLY167

TYR171

MET5

TYR59

GLU63

ASN66

TYR7

B Pocket

ALA24

VAL34

MET45

GLU63

ASN66

MET67

TYR7

HIS70

PHE9

TYR99

C Pocket

HIS70

THR73

ASP74

PHE9

ILE97

D Pocket

ARG114

GLN155

ARG156

TYR159

LEU160

TYR99

E Pocket

ARG114

TRP147

ALA152

ARG156

ILE97

F Pocket

ASP116

TYR123

THR143

LYS146

TRP147

ASN77

THR80

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 MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-A01:01 IPD-IMGT/HLA* [ipd-imgt:HLA34767]	10 20 30 40 50 60 GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQKMEPRAPWIEQEGPEYW 70 80 90 100 110 120 DQETRNMKAHSQTDRANLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYDG 130 140 150 160 170 180 KDYIALNEDLRSWTAADMAAQITKRKWEAVHAAEQRRVYLEGRCVDGLRRYLENGKETLQ 190 200 210 220 230 240 RTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT 250 260 270 280 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWELSSQPTIPI

3. Peptide	CTELKLNDY

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

Data can be downloaded to your local machine from the links below.

Clicking on the clipboard icon will copy the url for the data to your clipboard.

This can then be used to load the structure/data directly from the url into an application like PyMol (for 3D structures) using the load command:

e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif

or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.

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]

Components

MHC Class I alpha chain [cif]

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

Peptide only [cif]

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/4nqx

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.