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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.

Information sections


Complex type

Class i with peptide

1. Beta 2 microglobulin
['B']
2. Class I alpha
H2-Kb
['A']
3. Peptide
SAPDTRPA
['P']

Species


Locus / Allele group


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.
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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]
  1. 1G7Q assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 1G7Q assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 1G7Q assembly 1  
Peptide only [cif]
  1. 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