Alpha This is a work in progress and may change. Your feedback is very welcome.
  


5NQ3

SLA-1*14:02 binding "EFEDLTFLA" at 1.57Å 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.

Information sections


Complex type

Class i with peptide

1. Beta 2 microglobulin
['B', 'E']
2. Class I alpha
SLA-1*14:02
['A', 'D']
3. Peptide
EFEDLTFLA
['C', 'F']

Species


Locus / Allele group


Publication

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig.

Tungatt K, Dolton G, Morgan SB, Attaf M, Fuller A, Whalley T, Hemmink JD, Porter E, Szomolay B, Montoya M, Hammond JA, Miles JJ, Cole DK, Townsend A, Bailey M, Rizkallah PJ, Charleston B, Tchilian E, Sewell AK
PLoS Pathog. (2018) 14, e1007017 [doi:10.1371/journal.ppat.1007017]  [pubmed:29772011

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens.

Structure deposition and release

Deposited: 2017-04-19
Released: 2018-04-25
Revised: 2019-05-08

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: EFEDLTFLA

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

TYR8
SER168
LEU6
ARG171
ASN67
TYR172
TYR100
TYR60
TYR160
ASN64
THR164
PHE34
ARG63
P2 PHE

TYR100
TYR160
ASN64
ALA25
SER10
MET46
SER71
VAL68
PHE23
ASN67
TRP98
TYR8
P3 GLU

TYR100
TYR160
SER71
TRP157
ASN67
TRP98
P4 ASP

ASN67
P5 LEU

HIS156
TRP157
P6 THR

SER71
ASN75
TRP98
ILE74
ASN78
P7 PHE

TRP157
ASN78
TRP148
ALA153
HIS156
ALA151
ILE74
P8 LEU

ASN78
TRP148
VAL77
ILE74
LYS147
P9 ALA

LYS147
ASN78
SER144
LEU82
TRP148
TYR124
ILE143
THR81
TYR85

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

SER159
GLY163
GLU167
ARG171
SER5
GLU59
ARG63
ARG66
SER7
B Pocket

ILE24
PHE34
ARG45
ARG63
ARG66
ASN67
SER7
GLY70
PHE9
MET99
C Pocket

GLY70
GLN73
ILE74
PHE9
GLN97
D Pocket

TYR114
GLU155
HIS156
SER159
TYR160
MET99
E Pocket

TYR114
LYS147
ASP152
HIS156
GLN97
F Pocket

GLN116
ASP123
ILE143
ARG146
LYS147
VAL77
LYS80
THR81
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
SLA-1*14:02
        10        20        30        40        50        60
MGPHSLSYFSTAVSRPDRGDSRFIAVGYVDDTQFVRFDSDAPNPRMEPRAPWIQQEGQEY
        70        80        90       100       110       120
WDRNTRNVMGSAQINRVNLKTLRGYYNQSEAGSHTLQWMYGCYLGPDGLLLRGYDQFAYD
       130       140       150       160       170       180
GADYLALNEDLRSWTAADMAAQISKRKWEAADAAEHWRSYLQGTCVESLRRYLQMGKDTL
       190       200       210       220       230       240
QRAEPPKTHVTRHPSSDLGVTLRCWALGFHPKEISLTWQREGQDQSQDMELVETRPSGDG
       250       260       270
TFQKWAALVVPPGEEQSYTCHVQHEGLQEPLTLRWD

3. Peptide
EFEDLTFLA


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]
  1. 5NQ3 assembly 1  
  2. 5NQ3 assembly 2  

Components

MHC Class I alpha chain [cif]
  1. 5NQ3 assembly 1  
  2. 5NQ3 assembly 2  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 5NQ3 assembly 1  
  2. 5NQ3 assembly 2  
Peptide only [cif]
  1. 5NQ3 assembly 1  
  2. 5NQ3 assembly 2  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/5nq3

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