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6JTO

HLA-C*05:01 binding "GADGVGKSAL" at 1.70Å 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
HLA-C*05:01
['A']
3. Peptide
GADGVGKSAL
['C']

Species


Locus / Allele group


Publication

Rational discovery of a cancer neoepitope harboring the KRAS G12D driver mutation.

Bai P, Zhou Q, Wei P, Bai H, Chan SK, Kappler JW, Marrack P, Yin L
Sci China Life Sci (2021) [doi:10.1007/s11427-020-1888-1]  [pubmed:33740187

Cytotoxic T cells targeting cancer neoantigens harboring driver mutations can lead to durable tumor regression in an HLAI-dependent manner. However, it is difficult to extend the population of patients who are eligible for neoantigen-based immunotherapy, as immunogenic neoantigen-HLA pairs are rarely shared across different patients. Thus, a way to find other human leukocyte antigen (HLA) alleles that can also present a clinically effective neoantigen is needed. Recently, neoantigen-based immunotherapy targeting the KRAS G12D mutation in patients with HLA-C*08:02 has shown effectiveness. In a proof-of-concept study, we proposed a combinatorial strategy (the combination of phylogenetic and structural analyses) to find potential HLA alleles that could also present KRAS G12D neoantigen. Compared to in silico binding prediction, this strategy avoids the uneven accuracy across different HLA alleles. Our findings extend the population of patients who are potentially eligible for immunotherapy targeting the KRAS G12D mutation. Additionally, we provide an alternative way to predict neoantigen-HLA pairs, which maximizes the clinical usage of shared neoantigens.

Structure deposition and release

Deposited: 2019-04-11
Released: 2020-04-15
Revised: 2021-05-19

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Decamer (10 amino acids)

Sequence: GADGVGKSAL

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 GLY

GLU63
TRP167
MET5
PHE33
TYR171
TYR159
TYR59
TYR7
LYS66
P10 LEU

ASN77
TYR84
TRP147
THR143
TYR123
LEU95
LYS146
ILE124
LEU81
LYS80
PHE116
P2 ALA

TYR67
TYR9
TYR159
TYR7
LYS66
TYR99
GLU63
TRP167
P3 ASP

TYR9
TYR159
TYR99
LYS66
ARG156
ARG97
P4 GLY

ARG69
LYS66
P5 VAL

ARG69
ARG156
GLN155
P6 GLY

GLN155
ARG69
P7 LYS

GLU152
GLN155
THR73
GLN72
ARG69
P8 SER

PHE116
ASN77
ARG156
TRP147
GLU152
THR73
ARG97
P9 ALA

TRP147
ASN77
THR143
LYS146
THR73

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

LEU159
CYS163
LEU167
LEU171
ARG5
TRP59
THR63
TYR66
PHE7
B Pocket

VAL24
GLN34
GLU45
THR63
TYR66
LYS67
PHE7
ALA70
THR9
GLY99
C Pocket

ALA70
ASP73
ARG74
THR9
MET97
D Pocket

GLN114
ARG155
ARG156
LEU159
GLU160
GLY99
E Pocket

GLN114
GLU147
ALA152
ARG156
MET97
F Pocket

ALA116
ILE123
GLN143
TRP146
GLU147
LEU77
LEU80
ARG81
TYR84
GLN95

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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRD

2. Class I alpha
HLA-C*05:01
IPD-IMGT/HLA
[ipd-imgt:HLA35265]
        10        20        30        40        50        60
SHSMRYFYTAVSRPGRGEPRFIAVGYVDDTQFVQFDSDAASPRGEPRAPWVEQEGPEYWD
        70        80        90       100       110       120
RETQKYKRQAQTDRVNLRKLRGYYNQSEAGSHTLQRMYGCDLGPDGRLLRGYNQFAYDGK
       130       140       150       160       170       180
DYIALNEDLRSWTAADKAAQITQRKWEAAREAEQRRAYLEGTCVEWLRRYLENGKKTLQR
       190       200       210       220       230       240
AEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTF
       250       260       270
QKWAAVVVPSGEEQRYTCHVQHEGLPEPLTLRW

3. Peptide
GADGVGKSAL


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

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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. 6JTO assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 6JTO assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 6JTO assembly 1  
Peptide only [cif]
  1. 6JTO assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/6jto

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