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3P9L

H2-Kb binding "SIINFEKL" 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.

Information sections


Complex type

Class i with peptide

1. Beta 2 microglobulin
['B', 'E']
2. Class I alpha
H2-Kb
['A', 'D']
3. Peptide
SIINFEKL
['C', 'F']

Species


Locus / Allele group


Publication

Affinity thresholds for naive CD8+ CTL activation by peptides and engineered influenza A viruses.

Denton AE, Wesselingh R, Gras S, Guillonneau C, Olson MR, Mintern JD, Zeng W, Jackson DC, Rossjohn J, Hodgkin PD, Doherty PC, Turner SJ
J. Immunol. (2011) 187, 5733-44 [doi:10.4049/jimmunol.1003937]  [pubmed:22039305

High-avidity interactions between TCRs and peptide + class I MHC (pMHCI) epitopes drive CTL activation and expansion. Intriguing questions remain concerning the constraints determining optimal TCR/pMHCI binding. The present analysis uses the TCR transgenic OT-I model to assess how varying profiles of TCR/pMHCI avidity influence naive CTL proliferation and the acquisition of effector function following exposure to the cognate H-2K(b)/OVA(257-264) (SIINFEKL) epitope and to mutants provided as peptide or in engineered influenza A viruses. Stimulating naive OT-I CD8(+) T cells in vitro with SIINFEKL induced full CTL proliferation and differentiation that was largely independent of any need for costimulation. By contrast, in vitro activation with the low-affinity EIINFEKL or SIIGFEKL ligands depended on the provision of IL-2 and other costimulatory signals. Importantly, although they did generate potent endogenous responses, infection of mice with influenza A viruses expressing these same OVA(257) variants failed to induce the activation of adoptively transferred naive OT-I CTLps, an effect that was only partially overcome by priming with a lipopeptide vaccine. Subsequent structural and biophysical analysis of H2-K(b)OVA(257), H2-K(b)E1, and H2-K(b)G4 established that these variations introduce small changes at the pMHCI interface and decrease epitope stability in ways that would likely impact cell surface presentation and recognition. Overall, it seems that there is an activation threshold for naive CTLps, that minimal alterations in peptide sequence can have profound effects, and that the antigenic requirements for the in vitro and in vivo induction of CTL proliferation and effector function differ substantially.

Structure deposition and release

Deposited: 2010-10-18
Released: 2011-10-19
Revised: 2013-06-19

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Octamer (8 amino acids)

Sequence: SIINFEKL

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 SER

TYR59
TYR7
THR163
ARG62
GLU63
LYS66
LEU5
TYR171
TRP167
TYR159
P2 ILE

GLU24
TYR159
TYR7
ASN70
GLU63
LYS66
TYR45
VAL9
P3 ILE

GLN114
LEU156
ARG155
SER99
TYR159
ASN70
LYS66
P4 ASN

ASN70
LYS66
ARG155
P5 PHE

VAL97
SER99
GLU24
PHE74
TYR22
TYR116
SER73
ASN70
VAL9
GLN114
ARG155
P6 GLU

TRP147
ASP77
GLU152
ARG155
TYR116
SER73
P7 LYS

TRP147
ASP77
LYS146
SER73
VAL76
P8 LEU

ILE95
ASP77
TRP147
ILE142
TYR84
THR143
LYS146
TYR123
TYR116
THR80
LEU81

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
THR163
TRP167
TYR171
LEU5
TYR59
GLU63
LYS66
TYR7
B Pocket

GLU24
VAL34
TYR45
GLU63
LYS66
ALA67
TYR7
ASN70
VAL9
SER99
C Pocket

ASN70
SER73
PHE74
VAL9
VAL97
D Pocket

GLN114
ARG155
LEU156
TYR159
LEU160
SER99
E Pocket

GLN114
TRP147
GLU152
LEU156
VAL97
F Pocket

TYR116
TYR123
THR143
LYS146
TRP147
ASP77
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
IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDW
        70        80        90
SFYILAHTEFTPTETDTYACRVKHDSMAEPKTVYWDRDM

2. Class I alpha
H2-Kb
        10        20        30        40        50        60
GPHSLRYFVTAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWMEQEGPEYW
        70        80        90       100       110       120
ERETQKAKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQQYAYDG
       130       140       150       160       170       180
CDYIALNEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRYLKNGNATLL
       190       200       210       220       230       240
RTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLTWQLNGEELIQDMELVETRPAGDGT
       250       260       270
FQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPP

3. Peptide
SIINFEKL


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.
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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. 3P9L assembly 1  
  2. 3P9L assembly 2  

Components

MHC Class I alpha chain [cif]
  1. 3P9L assembly 1  
  2. 3P9L assembly 2  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 3P9L assembly 1  
  2. 3P9L assembly 2  
Peptide only [cif]
  1. 3P9L assembly 1  
  2. 3P9L assembly 2  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/3p9l

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