4N8V

HLA-A*11:01 binding "MLIYSMWGK" with KIR 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 kir

1. Beta 2 microglobulin

['B', 'E']

2. Class I alpha
HLA-A*11:01

['A', 'D']

3. Killer Ig-Like Receptors

['G', 'I']

4. Peptide
MLIYSMWGK

['C', 'F']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-A / HLA-A*11

Publication

Activating killer cell immunoglobulin-like receptor 2DS2 binds to HLA-A*11.

Liu J, Xiao Z, Ko HL, Shen M, Ren EC

Proc. Natl. Acad. Sci. U.S.A. (2014) 111, 2662-7 [doi:10.1073/pnas.1322052111] [pubmed:24550293]

Inhibitory killer cell Ig-like receptors (KIRs) are known to recognize HLA ligands mainly of the HLA-C and Bw4 groups, but the ligands for KIRs are poorly understood. We report here the identification of the cognate ligand for the activating KIR 2DS2 as HLA-A*11:01. The crystal structure of the KIR2DS2-HLA-A*11:01 complex was solved at 2.5-Å resolution and revealed residue-binding characteristics distinct from those of inhibitory KIRs with HLA-C and the critical role of residues Tyr45 and Asp72 in shaping binding specificity to HLA-A*11:01. Using KIR2DS2 tetramers, binding to surface HLA-A*11:01 on live cells was demonstrated and, furthermore, that binding can be altered by residue changes at p8 of the peptide, indicating the influence of peptide sequence on KIR-HLA association. In addition, heteronuclear single quantum coherence NMR was used to map the involvement of critical residues in HLA binding at the interface of KIR and HLA, and validates the data observed in the crystal structure. Our data provide structural evidence of the recognition of A*11:01 by the activating KIR2DS2 and extend our understanding of the KIR-HLA binding spectrum.

Structure deposition and release

Deposited: 2013-10-18

Released: 2014-02-05

Revised: 2014-03-12

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: MLIYSMWGK

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 MET

TYR59

TYR7

GLU63

TYR171

TRP167

PHE33

MET5

TYR159

ARG163

GLN62

P2 LEU

VAL67

TYR159

ARG163

TYR99

TYR9

ASN66

MET45

GLU63

TYR7

P3 ILE

GLN156

GLN155

TYR159

ARG163

GLN70

TYR99

TYR9

ASN66

ARG114

P4 TYR

ARG163

ASN66

P5 SER

GLN155

GLN70

ARG114

P6 MET

GLN70

THR73

ASN66

ALA69

GLN155

P7 TRP

THR73

TRP133

HIS151

ARG114

ALA152

ASP77

GLN156

TRP147

ALA150

GLN155

P8 GLY

THR73

ASP77

THR143

LYS146

TRP147

P9 LYS

TYR84

TYR123

ILE124

THR143

THR80

ASP116

ASP77

LYS146

TRP147

ILE142

LEU81

ARG114

ILE97

ILE95

ASP74

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

ARG163

TRP167

TYR171

MET5

TYR59

GLU63

ASN66

TYR7

B Pocket

ALA24

VAL34

MET45

GLU63

ASN66

VAL67

TYR7

GLN70

TYR9

TYR99

C Pocket

GLN70

THR73

ASP74

TYR9

ILE97

D Pocket

ARG114

GLN155

GLN156

TYR159

LEU160

TYR99

E Pocket

ARG114

TRP147

ALA152

GLN156

ILE97

F Pocket

ASP116

TYR123

THR143

LYS146

TRP147

ASP77

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 MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-A11:01 IPD-IMGT/HLA* [ipd-imgt:HLA34732]	10 20 30 40 50 60 GSHSMRYFYTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW 70 80 90 100 110 120 DQETRNVKAQSQTDRVDLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYDG 130 140 150 160 170 180 KDYIALNEDLRSWTAADMAAQITKRKWEAAHAAEQQRAYLEGRCVEWLRRYLENGKETLQ 190 200 210 220 230 240 RTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRW

3. Killer Ig-Like Receptors Killer Ig-Like Receptors	10 20 30 40 50 60 MHEGVHRKPSLLAHPGPLVKSEETVILQCWSDVRFEHFLLHREGKYKDTLHLIGEHHDGV 70 80 90 100 110 120 SKANFSIGPMMQDLAGTYRCYGSVTHSPYQLSAPSDPLDIVITGLYEKPSLSAQPGPTVL 130 140 150 160 170 180 AGESVTLSCSSRSSYDMYHLSREGEAHERRFSAGPKVNGTFQADFPLGPATHGGTYRCFG 190 200 SFRDSPYEWSNSSDPLLVSVT

4. Peptide	MLIYSMWGK

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]

Components

MHC Class I alpha chain [cif]

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

Peptide only [cif]

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/4n8v

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

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.