1G7Q

H2-Kb binding "SAPDTRPA" at 1.60Å 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']

2. Class I alpha
H2-Kb

['A']

3. Peptide
SAPDTRPA

['P']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-K / H2-Kb

Publication

Crystal structure of a non-canonical low-affinity peptide complexed with MHC class I: a new approach for vaccine design.

Apostolopoulos V, Yu M, Corper AL, Teyton L, Pietersz GA, McKenzie IF, Wilson IA, Plebanski M

J. Mol. Biol. (2002) 318, 1293-305 [doi:10.1016/s0022-2836(02)00196-1] [pubmed:12083518]

Peptides bind with high affinity to MHC class I molecules by anchoring certain side-chains (anchors) into specificity pockets in the MHC peptide-binding groove. Peptides that do not contain these canonical anchor residues normally have low affinity, resulting in impaired pMHC stability and loss of immunogenicity. Here, we report the crystal structure at 1.6 A resolution of an immunogenic, low-affinity peptide from the tumor-associated antigen MUC1, bound to H-2Kb. Stable binding is still achieved despite small, non-canonical residues in the C and F anchor pockets. This structure reveals how low-affinity peptides can be utilized in the design of novel peptide-based tumor vaccines. The molecular interactions elucidated in this non-canonical low-affinity peptide MHC complex should help uncover additional immunogenic peptides from primary protein sequences and aid in the design of alternative approaches for T-cell vaccines.

Structure deposition and release

Deposited: 2000-11-13

Released: 2002-07-17

Revised: 2020-07-29

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: SAPDTRPA

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

TYR7

TYR59

LYS66

LEU5

TYR159

ARG62

TRP167

TYR171

THR163

GLU63

P2 ALA

TYR159

TYR7

TYR45

GLU63

GLU24

LYS66

P3 PRO

ARG155

LYS66

GLN114

LEU156

TYR159

TYR7

ASN70

SER99

P4 ASP

ASN70

LYS66

ARG155

P5 THR

SER73

GLN114

PHE74

ASN70

TYR22

ARG155

TYR116

P6 ARG

ASP77

GLU152

ARG155

TYR116

SER73

TRP147

P7 PRO

SER73

TRP147

ASP77

VAL76

P8 ALA

TYR123

TRP147

ILE142

ASP77

THR80

TYR84

LYS146

THR143

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 FQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRW

3. Peptide	SAPDTRPA

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]

1G7Q assembly 1

Components

MHC Class I alpha chain [cif]

1G7Q assembly 1

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

1G7Q assembly 1

Peptide only [cif]

1G7Q assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/1g7q

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.