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1XR8

HLA-B*15:01 binding "LEKARGSTY" at 2.30Å 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*15:01
['A']
3. Peptide
LEKARGSTY
['C']

Species


Locus / Allele group


Publication

Crystal structures of two peptide-HLA-B*1501 complexes; structural characterization of the HLA-B62 supertype.

R��der G, Blicher T, Justesen S, Johannesen B, Kristensen O, Kastrup J, Buus S, Gajhede M
Acta Crystallogr. D Biol. Crystallogr. (2006) 62, 1300-10 [doi:10.1107/s0907444906027636]  [pubmed:17057332

MHC class I molecules govern human cytotoxic T cell responses. Their specificity determines which peptides they sample from the intracellular protein environment and then present to human cytotoxic T cells. More than 1100 different MHC class I proteins have been found in human populations and it would be a major undertaking to address each of these specificities individually. Based upon their peptide binding specificity, they are currently subdivided into 12 supertypes. Several of these HLA supertypes have not yet been described at the structural level. To support a comprehensive understanding of human immune responses, the structure of at least one member of each supertype should be determined. Here, the structures of two immunogenic peptide-HLA-B*1501 complexes are described. The structure of HLA-B*1501 in complex with a peptide (LEKARGSTY, corresponding to positions 274-282 in the Epstein-Barr virus nuclear antigen-3A) was determined to 2.3 A resolution. The structure of HLA-B*1501 in complex with a peptide (ILGPPGSVY) derived from human ubiquitin-conjugating enzyme-E2 corresponding to positions 91-99 was solved to 1.8 A resolution. Mutual comparisons of these two structures with structures from other HLA supertypes define and explain the specificity of the P2 and P9 peptide anchor preferences in the B62 HLA supertype. The P2 peptide residue binds to the B-pocket in HLA-B*1501. This pocket is relatively large because of the small Ser67 residue located at the bottom. The peptide proximal part of the B-pocket is hydrophobic, which is consistent with P2 anchor residue preference for Leu. The specificity of the B-pocket is determined by the Met45, Ile66 and Ser67 residues. The apex of the B-pocket is hydrophilic because of the Ser67 residue. The P9 peptide residue binds to the F-pocket in HLA-B*1501. The residues most important for the specificity of this pocket are Tyr74, Leu81, Leu95, Tyr123 and Trp147. These residues create a hydrophobic interior in the F-pocket and their spatial arrangement makes the pocket capable of containing large, bulky peptide side chains. Ser116 is located at the bottom of the F-pocket and makes the bottom of this pocket hydrophilic. Ser116, may act as a hydrogen-bonding partner and as such is a perfect place for binding of a Tyr9 peptide residue. Thus, based on structure information it is now possible to explain the peptide sequence specificity of HLA-B*1501 as previously determined by peptide binding and pool sequencing experiments.

Structure deposition and release

Deposited: 2004-10-14
Released: 2005-04-14
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: LEKARGSTY

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 LEU

TYR59
GLU63
TRP167
PHE33
TYR171
TYR7
CYS164
LEU163
MET5
ARG62
TYR159
P2 GLU

MET45
ASN70
TYR159
GLU63
ILE66
ARG62
TYR99
SER67
TYR9
TYR7
ALA24
P3 LYS

TYR99
TRP156
TYR159
ILE66
ARG62
GLU152
TYR9
GLN155
P4 ALA

ILE66
ARG62
P5 ARG

GLN155
P6 GLY

GLU152
THR73
P7 SER

GLU152
LYS146
TRP147
ARG97
ALA150
P8 THR

GLU76
THR73
LYS146
TRP147
SER77
ASN80
THR143
P9 TYR

ILE124
THR143
SER116
TYR84
TYR123
LEU95
LYS146
TYR74
ARG97
ASN80
GLN96
TRP147
LEU81
SER77

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
ILE66
TYR7
B Pocket

ALA24
VAL34
MET45
GLU63
ILE66
SER67
TYR7
ASN70
TYR9
TYR99
C Pocket

ASN70
THR73
TYR74
TYR9
ARG97
D Pocket

ASP114
GLN155
TRP156
TYR159
LEU160
TYR99
E Pocket

ASP114
TRP147
GLU152
TRP156
ARG97
F Pocket

SER116
TYR123
THR143
LYS146
TRP147
SER77
ASN80
LEU81
TYR84
LEU95

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-B*15:01
IPD-IMGT/HLA
[ipd-imgt:HLA35228]
        10        20        30        40        50        60
GSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRMAPRAPWIEQEGPEYW
        70        80        90       100       110       120
DRETQISKTNTQTYRESLRNLRGYYNQSEAGSHTLQRMYGCDVGPDGRLLRGHDQSAYDG
       130       140       150       160       170       180
KDYIALNEDLSSWTAADTAAQITQRKWEAAREAEQWRAYLEGLCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide
LEKARGSTY


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. 1XR8 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 1XR8 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 1XR8 assembly 1  
Peptide only [cif]
  1. 1XR8 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/1xr8

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