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3X12

HLA-B*57:01 binding "LSSPVTKSF" at 1.80Å 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
LSSPVTKSF
['C']

Species


Locus / Allele group


Publication

The Interaction of KIR3DL1*001 with HLA Class I Molecules Is Dependent upon Molecular Microarchitecture within the Bw4 Epitope.

Saunders PM, Vivian JP, Baschuk N, Beddoe T, Widjaja J, O'Connor GM, Hitchen C, Pymm P, Andrews DM, Gras S, McVicar DW, Rossjohn J, Brooks AG
J. Immunol. (2014) [doi:10.4049/jimmunol.1402542]  [pubmed:25480565

The killer cell Ig-like receptor 3DL1 (KIR3DL1) inhibits activation of NK cells upon interaction with HLA class I molecules such as HLA-B*57:01, which contains the Bw4 epitope spanning residues 77-83 (e.g., NLRIALR), and not with HLA allomorphs that possess the Bw6 motif (e.g., HLA-B*08:01), which differ at residues 77, 80, 81, 82, and 83. Although Bw4 residues Ile(80) and Arg(83) directly interact with KIR3DL1*001, their precise role in determining KIR3DL1-HLA-Bw4 specificity remains unclear. Recognition of HLA-B*57:01 by either KIR3DL1(+) NK cells or the NK cell line YTS transfected with KIR3DL1*001 was impaired by mutation of residues 80 and 83 of HLA-B*57:01 to the corresponding amino acids within the Bw6 motif. Conversely, the simultaneous introduction of three Bw4 residues at positions 80, 82, and 83 into HLA-B*08:01 conferred an interaction with KIR3DL1*001. Structural analysis of HLA-B*57:01, HLA-B*08:01, and mutants of each bearing substitutions at positions 80 and 83 revealed that Ile(80) and Arg(83) within the Bw4 motif constrain the conformation of Glu(76), primarily through a salt bridge between Arg(83) and Glu(76). This salt bridge was absent in HLA-Bw6 molecules as well as position 83 mutants of HLA-B*57:01. Mutation of the Bw4 residue Ile(80) also disrupted this salt bridge, providing further insight into the role that position 80 plays in mediating KIR3DL1 recognition. Thus, the strict conformation of HLA-Bw4 allotypes, held in place by the Glu(76)-Arg(83) interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the α1 helix that is less permissive for KIR3DL1 binding.

Structure deposition and release

Deposited: 2014-10-24
Released: 2014-12-24
Revised: 2015-04-08

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: LSSPVTKSF

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

TYR7
TRP167
MET5
CYS164
TYR171
PHE33
GLU63
TYR159
TYR59
LEU163
P2 SER

TYR99
GLU63
MET45
TYR159
ASN66
TYR7
MET67
TYR9
P3 SER

LEU156
TYR9
TYR99
SER70
TYR159
ASN66
P4 PRO

TYR159
ASN66
LEU163
P5 VAL

LEU156
VAL152
TYR159
GLN155
P6 THR

VAL152
GLN155
THR73
P7 LYS

TYR74
SER116
VAL152
ASN77
THR73
ASP114
TRP133
LEU156
TRP147
P8 SER

LYS146
ASN77
GLU76
THR73
THR143
TRP147
P9 PHE

TYR123
ASN80
ALA81
TYR74
LYS146
ASN77
TYR84
ILE95
ILE142
THR143
TRP147
SER116

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
ASN80
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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

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
DGETRNMKASAQTYRENLRNALRYYNQSEAGSHIIQVMYGCDVGPDGRLLRGHDQSAYDG
       130       140       150       160       170       180
KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide
LSSPVTKSF


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. 3X12 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 3X12 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 3X12 assembly 1  
Peptide only [cif]
  1. 3X12 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/3x12

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