5B39

HLA-B*57:01 binding "LSSPVTKSF" with KIR-3 NK receptor at 2.50Å 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.

Complex type

Class i with peptide and kir3

1. Beta 2 microglobulin

['B']

2. Class I alpha
HLA-B*57:01

['A']

3. kir3

['G']

4. Peptide
LSSPVTKSF

['C']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*57

Publication

Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition.

Saunders PM, Pymm P, Pietra G, Hughes VA, Hitchen C, O'Connor GM, Loiacono F, Widjaja J, Price DA, Falco M, Mingari MC, Moretta L, McVicar DW, Rossjohn J, Brooks AG, Vivian JP

J. Exp. Med. (2016) [doi:10.1084/jem.20152023] [pubmed:27045007]

Natural killer (NK) cells play a key role in immunity, but how HLA class I (HLA-I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism impacts disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognizing the widest array of HLA-I ligands. These differences were further reflected in functional studies using NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005, and *015 polymorphisms are remote from the KIR3DL1-HLA-I interface, the structures of these three KIR3DL1-HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.

Structure deposition and release

Deposited: 2016-02-12

Released: 2016-03-30

Revised: 2020-07-29

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

PHE33

TYR171

GLU63

LEU163

TYR159

TYR59

TYR7

MET5

TRP167

P2 SER

MET67

TYR9

MET45

TYR159

TYR99

ASN66

TYR7

GLU63

P3 SER

ASN66

LEU156

TYR9

TYR99

SER70

TYR159

P4 PRO

TYR159

ASN66

LEU163

P5 VAL

LEU156

GLN155

VAL152

TYR159

P6 THR

THR73

VAL152

P7 LYS

TRP133

LEU156

ASN77

TYR74

SER116

THR73

ASP114

VAL152

TRP147

P8 SER

LYS146

ASN77

THR73

TRP147

ILE80

THR143

P9 PHE

THR143

TYR123

LYS146

TYR74

SER116

ILE80

TYR84

ASN77

ILE95

ILE142

TRP147

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 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW 70 80 90 SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-B57:01 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. kir3 kir3	10 20 30 40 50 60 HVGGQDKPFLSAWPSAVVPRGGHVTLRCHYRHRFNNFMLYKEDRIHVPIFHGRLFQESFN 70 80 90 100 110 120 MSPVTTAHAGNYTCRGSHPHSPTGWSAPSNPVVIMVTGNHRKPSLLAHPGPLVKSGERVI 130 140 150 160 170 180 LQCWSDIMFEHFFLHKEGISKDPSRLVGQIHDGVSKANFSIGPMMLALAGTYRCYGSVTH 190 200 210 220 230 240 TPYQLSAPSDPLDIVVTGPYEKPSLSAQPGPKVQAGESVTLSCSSRSSYDMYHLSREGGA 250 260 270 280 290 HERRLPAVRKVNRTFQADFPLGPATHGGTYRCFGSFRHSPYEWSDPSDPLLVSVTGNPS

4. 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]

5B39 assembly 1

Components

MHC Class I alpha chain [cif]

5B39 assembly 1

MHC Class I antigen binding domain (alpha1/alpha2) [cif]

5B39 assembly 1

Peptide only [cif]

5B39 assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/5b39

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.

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Footnotes

Protein Data Bank Europe - Coordinate Server
1HHK - HLA-A*02:01 binding LLFGYPVYV at 2.5Å resolution - PDB entry for 1HHK
Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. - PyMol CEALIGN Method - Publication
PyMol - PyMol.org/pymol
Levenshtein distance - Wikipedia entry
Protein Data Bank Europe REST API - Molecules endpoint
3Dmol.js: molecular visualization with WebGL - 3DMol.js - Publication
Protein Data Bank Europe REST API - Publication endpoint
PubMed Central Europe REST API - Articles endpoint

This work is licensed under a Creative Commons Attribution 4.0 International License.