4IHO

H2-Db binding "EGPRNQDWL" at 2.80Å 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', 'E']

2. Class I alpha
H2-Db

['A', 'D']

3. Peptide
EGPRNQDWL

['C', 'F']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-D / H2-Db

Publication

Proline substitution independently enhances H-2D(b) complex stabilization and TCR recognition of melanoma-associated peptides.

Uchtenhagen H, Abualrous ET, Stahl E, Allerbring EB, Sluijter M, Zacharias M, Sandalova T, van Hall T, Springer S, Nygren PÅ, Achour A

Eur. J. Immunol. (2013) [doi:10.1002/eji.201343456] [pubmed:23939911]

The immunogenicity of H-2D(b) (D(b)) restricted epitopes can be significantly increased by substituting peptide position 3 to a proline (p3P). The p3P modification enhances MHC stability without altering the conformation of the modified epitope allowing for T-cell cross-reactivity with the native peptide. The present study reveals how specific interactions between p3P and the highly conserved MHC heavy chain residue Y159 increase the stability of D(b) in complex with an optimized version of the melanoma-associated epitope gp10025-33 . Furthermore, the p3P modification directly increased the affinity of the D(b)/gp10025-33 -specific T-cell receptor (TCR) pMel. Surprisingly, the enhanced TCR binding was independent from the observed increased stability of the optimized D(b)/gp10025-33 complex and from the interactions formed between p3P and Y159, indicating a direct effect of the p3P modification on TCR recognition.

Structure deposition and release

Deposited: 2012-12-19

Released: 2013-09-11

Revised: 2013-12-11

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: EGPRNQDWL

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

PHE159

TYR59

LYS66

GLU163

TRP167

GLU63

MET5

TYR171

TYR7

ARG62

P2 GLY

TYR7

PHE159

LYS66

GLU63

P3 PRO

GLU9

TYR7

SER99

PHE159

LYS66

GLN97

GLN70

P4 ARG

GLN70

LYS66

HIS155

TYR156

P5 ASN

TYR156

PHE74

GLN97

PHE116

GLN70

HIS155

TRP73

P6 GLN

ALA152

HIS155

GLY151

TRP73

TYR156

SER150

P7 ASP

LYS146

SER150

TYR156

TRP73

TRP147

P8 TRP

VAL76

SER77

TRP73

LYS146

TRP147

THR143

GLN72

P9 LEU

TRP147

THR143

LEU78

TYR123

ILE124

PHE116

LEU81

SER77

ASN80

TYR84

LEU95

TRP73

LYS146

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

PHE159

GLU163

TRP167

TYR171

MET5

TYR59

GLU63

LYS66

TYR7

B Pocket

SER24

VAL34

TYR45

GLU63

LYS66

ALA67

TYR7

GLN70

GLU9

SER99

C Pocket

GLN70

TRP73

PHE74

GLU9

GLN97

D Pocket

LEU114

HIS155

TYR156

PHE159

LEU160

SER99

E Pocket

LEU114

TRP147

ALA152

TYR156

GLN97

F Pocket

PHE116

TYR123

THR143

LYS146

TRP147

SER77

ASN80

LEU81

TYR84

LEU95

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-Db	10 20 30 40 50 60 GPHSMRYFETAVSRPGLEEPRYISVGYVDNKEFVRFDSDAENPRYEPRAPWMEQEGPEYW 70 80 90 100 110 120 ERETQKAKGQEQWFRVSLRNLLGYYNQSAGGSHTLQQMSGCDLGSDWRLLRGYLQFAYEG 130 140 150 160 170 180 RDYIALNEDLKTWTAADMAAQITRRKWEQSGAAEHYKAFLEGECVEWLHRYLKNGNATLL 190 200 210 220 230 240 RTDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGT 250 260 270 FQKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWEP

3. Peptide	EGPRNQDWL

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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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/4iho

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.