Alpha This is a work in progress and may change. Your feedback is very welcome.
  


6J2A

HLA-A*30:03 binding "CTELKLSDY" at 1.40Å 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-A*30:03
['A']
3. Peptide
CTELKLSDY
['C']

Species


Locus / Allele group


Publication

Divergent Peptide Presentations of HLA-A*30 Alleles Revealed by Structures With Pathogen Peptides.

Zhu S, Liu K, Chai Y, Wu Y, Lu D, Xiao W, Cheng H, Zhao Y, Ding C, Lyu J, Lou Y, Gao GF, Liu WJ
Front Immunol (2019) 10, 1709 [doi:10.3389/fimmu.2019.01709]  [pubmed:31396224

Human leukocyte antigen (HLA) alleles have a high degree of polymorphism, which determines their peptide-binding motifs and subsequent T-cell receptor recognition. The simplest way to understand the cross-presentation of peptides by different alleles is to classify these alleles into supertypes. A1 and A3 HLA supertypes are widely distributed in humans. However, direct structural and functional evidence for peptide presentation features of key alleles (e.g., HLA-A*30:01 and -A*30:03) are lacking. Herein, the molecular basis of peptide presentation of HLA-A*30:01 and -A*30:03 was demonstrated by crystal structure determination and thermostability measurements of complexes with T-cell epitopes from influenza virus (NP44), human immunodeficiency virus (RT313), and Mycobacterium tuberculosis (MTB). When binding to the HIV peptide, RT313, the PΩ-Lys anchoring modes of HLA-A*30:01, and -A*30:03 were similar to those of HLA-A*11:01 in the A3 supertype. However, HLA-A*30:03, but not -A*30:01, also showed binding with the HLA*01:01-favored peptide, NP44, but with a specific structural conformation. Thus, different from our previous understanding, HLA-A*30:01 and -A*30:03 have specific peptide-binding characteristics that may lead to their distinct supertype-featured binding peptide motifs. Moreover, we also found that residue 77 in the F pocket was one of the key residues for the divergent peptide presentation characteristics of HLA-A*30:01 and -A*30:03. Interchanging residue 77 between HLA-A*30:01 and HLA-A*30:03 switched their presented peptide profiles. Our results provide important recommendations for screening virus and tumor-specific peptides among the population with prevalent HLA supertypes for vaccine development and immune interventions.

Structure deposition and release

Deposited: 2018-12-31
Released: 2019-09-25
Revised: 2019-09-25

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: CTELKLSDY

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 CYS

TYR59
TYR7
THR163
GLU63
PHE33
MET5
TYR171
TYR159
TRP167
P2 THR

TYR159
ASN66
MET45
THR163
GLU63
TYR7
TYR99
VAL67
P3 GLU

GLU114
TYR159
ASN66
ARG152
LEU156
TYR99
P4 LEU

GLN62
ASN66
ALA69
P5 LYS

ARG152
P6 LEU

TYR99
HIS116
GLU114
ILE97
THR73
ARG152
HIS70
P7 SER

TRP147
ARG152
THR73
ASN77
P8 ASP

TRP147
GLU76
LYS146
THR143
THR73
ASN77
P9 TYR

ASN77
HIS116
THR143
TRP147
ILE124
ILE142
LEU81
THR80
ILE95
TYR123
LYS146
ILE97
TYR84

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
MET5
TYR59
GLU63
ASN66
TYR7
B Pocket

ALA24
VAL34
MET45
GLU63
ASN66
VAL67
TYR7
HIS70
SER9
TYR99
C Pocket

HIS70
THR73
ASP74
SER9
ILE97
D Pocket

GLU114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

GLU114
TRP147
ARG152
LEU156
ILE97
F Pocket

HIS116
TYR123
THR143
LYS146
TRP147
ASN77
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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-A*30:03
IPD-IMGT/HLA
[ipd-imgt:HLA00091]
        10        20        30        40        50        60
GSHSMRYFSTSVSRPGSGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DQETRNVKAHSQTDRENLGTLRGYYNQSEAGSHTIQIMYGCDVGSDGRFLRGYEQHAYDG
       130       140       150       160       170       180
KDYIALNEDLRSWTAADMAAQITQRKWEAARRAEQLRAYLEGTCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRW

3. Peptide
CTELKLSDY


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]
  1. 6J2A assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 6J2A assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 6J2A assembly 1  
Peptide only [cif]
  1. 6J2A assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/6j2a

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