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3BXN

HLA-B*14:02 binding "IRAAPPPLF" at 1.86Å 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*14:02
['A']
3. Peptide
IRAAPPPLF
['C']

Species


Locus / Allele group


Publication

Structural basis for T cell alloreactivity among three HLA-B14 and HLA-B27 antigens.

Kumar P, Vahedi-Faridi A, Saenger W, Merino E, López de Castro JA, Uchanska-Ziegler B, Ziegler A
J. Biol. Chem. (2009) 284, 29784-97 [doi:10.1074/jbc.M109.038497]  [pubmed:19617632

The existence of cytotoxic T cells (CTL) cross-reacting with the human major histocompatibility antigens HLA-B14 and HLA-B27 suggests that their alloreactivity could be due to presentation of shared peptides in similar binding modes by these molecules. We therefore determined the crystal structures of the subtypes HLA-B*1402, HLA-B*2705, and HLA-B*2709 in complex with a proven self-ligand, pCatA (peptide with the sequence IRAAPPPLF derived from cathepsin A (residues 2-10)), and of HLA-B*1402 in complex with a viral peptide, pLMP2 (RRRWRRLTV, derived from latent membrane protein 2 (residues 236-244) of Epstein-Barr virus). Despite the exchange of 18 residues within the binding grooves of HLA-B*1402 and HLA-B*2705 or HLA-B*2709, the pCatA peptide is presented in nearly identical conformations. However, pLMP2 is displayed by HLA-B*1402 in a conformation distinct from those previously found in the two HLA-B27 subtypes. In addition, the complexes of HLA-B*1402 with the two peptides reveal a nonstandard, tetragonal mode of the peptide N terminus anchoring in the binding groove because of the exchange of the common Tyr-171 by His-171 of the HLA-B*1402 heavy chain. This exchange appears also responsible for reduced stability of HLA-B14-peptide complexes in vivo and slow assembly in vitro. The studies with the pCatA peptide uncover that CTL cross-reactive between HLA-B14 and HLA-B27 might primarily recognize the common structural features of the bound peptide, thus neglecting amino acid replacements within the rim of the binding grooves. In contrast, structural alterations between the three complexes with the pLMP2 peptide indicate how heavy chain polymorphisms can influence peptide display and prevent CTL cross-reactivity between HLA-B14 and HLA-B27 antigens.

Structure deposition and release

Deposited: 2008-01-14
Released: 2009-02-03
Revised: 2011-07-13

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: IRAAPPPLF

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 ILE

TYR59
ASN63
ILE66
MET5
TYR159
THR163
ARG62
TRP167
TYR7
HIS171
P2 ARG

VAL34
TYR159
TYR7
VAL25
CYS67
GLU45
TYR99
ASN63
ARG35
ILE66
GLY26
PHE36
SER24
TYR9
P3 ALA

TYR9
TYR159
TRP97
TYR99
ILE66
P4 ALA

ASN70
ILE66
TRP97
P5 PRO

THR69
THR73
ASN70
GLU152
ILE66
TRP97
P6 PRO

TRP147
TRP97
PHE116
THR73
ASN70
GLU152
P7 PRO

GLU152
TRP147
ALA150
SER77
P8 LEU

TRP147
ASN80
GLU76
LYS146
SER77
THR73
P9 PHE

SER77
PHE116
ILE142
THR143
TRP147
LEU95
ASN80
ILE124
TYR123
LEU81
TYR84
LYS146

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

ALA159
GLY163
GLU167
ARG171
SER5
GLU59
ARG63
GLN66
ARG7
B Pocket

ILE24
PHE34
ARG45
ARG63
GLN66
ILE67
ARG7
THR70
PHE9
MET99
C Pocket

THR70
GLN73
THR74
PHE9
GLN97
D Pocket

TYR114
GLU155
GLN156
ALA159
TYR160
MET99
E Pocket

TYR114
LYS147
ARG152
GLN156
GLN97
F Pocket

GLN116
ASP123
ILE143
ARG146
LYS147
GLU77
ARG80
ASN81
GLY84
THR95

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*14:02
IPD-IMGT/HLA
[ipd-imgt:HLA32021]
        10        20        30        40        50        60
MGSHSMRYFYTAVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPREEPRAPWIEQEGPEY
        70        80        90       100       110       120
WDRNTQICKTNTQTDRESLRNLRGYYNQSEAGSHTLQWMYGCDVGPDGRLLRGYNQFAYD
       130       140       150       160       170       180
GKDYIALNEDLSSWTAADTAAQITQRKWEAAREAEQLRAYLEGTCVEWLRRHLENGKETL
       190       200       210       220       230       240
QRADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDR
       250       260       270
TFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEPS

3. Peptide
IRAAPPPLF


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. 3BXN assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 3BXN assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 3BXN assembly 1  
Peptide only [cif]
  1. 3BXN assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/3bxn

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