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6D2R

HLA-B*57:01 binding "GSFDYSGVHLW" at 1.83Å 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-B*57:01
['A']
3. Peptide
GSFDYSGVHLW
['C']

Species


Locus / Allele group


Publication

A subset of HLA-I peptides are not genomically templated: Evidence for cis- and trans-spliced peptide ligands.

Faridi P, Li C, Ramarathinam SH, Vivian JP, Illing PT, Mifsud NA, Ayala R, Song J, Gearing LJ, Hertzog PJ, Ternette N, Rossjohn J, Croft NP, Purcell AW
Sci Immunol (2018) 3, [doi:10.1126/sciimmunol.aar3947]  [pubmed:30315122

The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i.e., the fusion of peptide segments from distinct antigens) are also bound and presented by HLA molecules, and if so, in what proportion. Here, we have developed and applied a bioinformatic workflow and demonstrated that trans-spliced peptides are presented by HLA-I, and their abundance challenges current models of proteasomal splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA-binding sequence features and are as frequently identified as cis-spliced peptides found bound to a number of different HLA-A and HLA-B allotypes. Structural analysis reveals that the junction between spliced peptides is highly solvent exposed and likely to participate in T cell receptor interactions. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design, and immunotherapy.

Structure deposition and release

Deposited: 2018-04-13
Released: 2018-10-03
Revised: 2019-04-17

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Undecamer (11 amino acids)

Sequence: GSFDYSGVHLW

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

MET5
TYR159
TYR59
TYR7
TRP167
PHE33
TYR171
GLU63
P10 LEU

TRP147
THR143
ASN77
LYS146
THR73
GLU76
ILE80
P11 TRP

THR143
TYR118
TYR123
ALA81
LYS146
TYR74
SER116
ALA117
ILE80
TYR84
ASN77
ILE95
TRP147
ILE142
P2 SER

TYR99
TYR9
GLU63
MET45
TYR159
TYR7
ASN66
MET67
P3 PHE

TYR9
LEU156
GLN155
SER70
TYR159
TYR99
ASN66
P4 ASP

GLN155
ASN66
P5 TYR

LEU156
GLN155
ALA150
VAL152
P6 SER

GLN155
P7 GLY

GLN155
P8 VAL

VAL152
P9 HIS

VAL152
ASN77
TYR74
THR73
TRP147
LEU156

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
LEU163
TRP167
TYR171
MET5
TYR59
GLU63
ASN66
TYR7
B Pocket

ALA24
VAL34
MET45
GLU63
ASN66
MET67
TYR7
SER70
TYR9
TYR99
C Pocket

SER70
THR73
TYR74
TYR9
VAL97
D Pocket

ASP114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

ASP114
TRP147
VAL152
LEU156
VAL97
F Pocket

SER116
TYR123
THR143
LYS146
TRP147
ASN77
ILE80
ALA81
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
MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD
        70        80        90
WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-B*57:01
IPD-IMGT/HLA
[ipd-imgt:HLA34051]
        10        20        30        40        50        60
GSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRMAPRAPWIEQEGPEYW
        70        80        90       100       110       120
DGETRNMKASAQTYRENLRIALRYYNQSEAGSHIIQVMYGCDVGPDGRLLRGHDQSAYDG
       130       140       150       160       170       180
KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide
GSFDYSGVHLW


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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Complete structures

Aligned structures [cif]
  1. 6D2R assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 6D2R assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 6D2R assembly 1  
Peptide only [cif]
  1. 6D2R assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/6d2r

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