7DUU

HLA-C*01:02 binding "LNPSVAATL" with KIR NK receptor at 2.51Å 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']

2. Class I alpha
HLA-C*01:02

['A']

3. Killer Ig-Like Receptors

['D']

4. Peptide
LNPSVAATL

['C']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-C / HLA-C*01

Publication

Activating receptor KIR2DS2 bound to HLA-C1 reveals the novel recognition features of activating receptor.

Yang Y, Bai H, Wu Y, Chen P, Zhou J, Lei J, Ye X, Brown AJ, Zhou X, Shu T, Chen Y, Wei P, Yin L

Immunology (2021) [doi:10.1111/imm.13439] [pubmed:34967442]

Killer cell immunoglobulin-like receptors (KIRs) are important receptors for regulating the killing of virus-infected or cancer cells of natural killer (NK) cells. KIR2DS2 can recognize peptides derived from hepatitis C virus (HCV) or global flaviviruses (such as dengue and Zika) presented by HLA-C*0102 to activate NK cells, and has shown promising results when used for cancer immunotherapy. Here, we present the complex structure of KIR2DS2 with HLA-C*0102 at a resolution of 2·5Å. Our structure reveals that KIR2DS2 can bind with HLA-C*0102 and HLA-A*1101 in two different directions. Moreover, Tyr45 (in activating receptor KIR2DS2) and Phe45 (in inhibitory KIRs) distinguish the two different binding models and binding affinity between activating KIRs and inhibitory KIRs. The conserved 'AT' motif of the peptide mediates recognition and determines the peptide specificity of recognition. These structural characteristics shed light on how KIRs activate NK cells and can provide a molecular basis for immunotherapy by NK cells.

Structure deposition and release

Deposited: 2021-01-11

Released: 2022-02-02

Revised: 2022-02-23

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: LNPSVAATL

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

THR163

ARG62

TYR59

LYS66

TYR7

GLU63

TYR171

MET5

TRP167

PHE33

TYR159

P2 ASN

TYR67

TYR159

SER24

VAL34

LYS66

TYR7

PHE9

GLU63

P3 PRO

GLN70

CYS99

LYS66

PHE9

TRP97

TYR159

TYR7

P4 SER

TRP97

TYR159

GLN70

LYS66

P5 VAL

LYS66

THR73

ARG69

GLN70

P6 ALA

THR73

TYR116

GLN70

GLU152

ARG156

TRP97

P7 ALA

THR73

SER77

TRP147

GLU152

ARG156

P8 THR

VAL76

ASN80

THR73

TRP147

SER77

P9 LEU

LYS146

THR143

TYR116

LEU81

LEU95

ASN80

TRP147

TYR84

TYR123

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

LEU159

CYS163

LEU167

LEU171

LYS5

TRP59

THR63

TYR66

PHE7

B Pocket

VAL24

ARG34

GLU45

THR63

TYR66

LYS67

PHE7

ALA70

THR9

GLY99

C Pocket

ALA70

ASP73

ARG74

THR9

MET97

D Pocket

GLN114

ARG155

ARG156

LEU159

GLU160

GLY99

E Pocket

GLN114

GLU147

ALA152

ARG156

MET97

F Pocket

ALA116

ILE123

GLN143

TRP146

GLU147

LEU77

LEU80

ARG81

TYR84

GLN95

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-C01:02 IPD-IMGT/HLA* [ipd-imgt:HLA35377]	10 20 30 40 50 60 SHSMKYFFTSVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPRGEPRAPWVEQEGPEYWD 70 80 90 100 110 120 RETQKYKRQAQTDRVSLRNLRGYYNQSEAGSHTLQWMCGCDLGPDGRLLRGYDQYAYDGK 130 140 150 160 170 180 DYIALNEDLRSWTAADTAAQITQRKWEAAREAEQRRAYLEGTCVEWLRRYLENGKETLQR 190 200 210 220 230 240 AEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTF 250 260 270 QKWAAVMVPSGEEQRYTCHVQHEGLPEPLTLRW

3. Killer Ig-Like Receptors Killer Ig-Like Receptors	10 20 30 40 50 60 HEGVHRKPSLLAHPGPLVKSEETVILQCWSDVRFEHFLLHREGKYKDTLHLIGEHHDGVS 70 80 90 100 110 120 KANFSIGPMMQDLAGTYRCYGSVTHSPYQLSAPSDPLDIVITGLYEKPSLSAQPGPTVLA 130 140 150 160 170 180 GESVTLSCSSRSSYDMYHLSREGEAHERRFSAGPKVNGTFQADFPLGPATHGGTYRCFGS 190 FRDSPYEWSNSSDPLLVSVT

4. Peptide	LNPSVAATL

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]

7DUU assembly 1

Components

MHC Class I alpha chain [cif]

7DUU assembly 1

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

7DUU assembly 1

Peptide only [cif]

7DUU assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/7duu

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.