2DYP

HLA-G*01:01 binding "RIIPRHLQL" with LIR-2 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 lir2

1. Beta 2 microglobulin

['B']

2. Class I alpha
HLA-G*01:01

['A']

3. LIR-2

['D']

4. Peptide
RIIPRHLQL

['C']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-G / HLA-G*01

Publication

Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d).

Shiroishi M, Kuroki K, Rasubala L, Tsumoto K, Kumagai I, Kurimoto E, Kato K, Kohda D, Maenaka K

Proc. Natl. Acad. Sci. U.S.A. (2006) 103, 16412-7 [doi:10.1073/pnas.0605228103] [pubmed:17056715]

HLA-G is a nonclassical MHC class I (MHCI) molecule that can suppress a wide range of immune responses in the maternal-fetal interface. The human inhibitory immune receptors leukocyte Ig-like receptor (LILR) B1 [also called LIR1, Ig-like transcript 2 (ILT2), or CD85j] and LILRB2 (LIR2/ILT4/CD85d) preferentially recognize HLA-G. HLA-G inherently exhibits various forms, including beta(2)-microglobulin (beta(2)m)-free and disulfide-linked dimer forms. Notably, LILRB1 cannot recognize the beta(2)m-free form of HLA-G or HLA-B27, but LILRB2 can recognize the beta(2)m-free form of HLA-B27. To date, the structural basis for HLA-G/LILR recognition remains to be examined. Here, we report the 2.5-A resolution crystal structure of the LILRB2/HLA-G complex. LILRB2 exhibits an overlapping but distinct MHCI recognition mode compared with LILRB1 and dominantly recognizes the hydrophobic site of the HLA-G alpha3 domain. NMR binding studies also confirmed these LILR recognition differences on both conformed (heavy chain/peptide/beta(2)m) and free forms of beta(2)m. Binding studies using beta(2)m-free MHCIs revealed differential beta(2)m-dependent LILR-binding specificities. These results suggest that subtle structural differences between LILRB family members cause the distinct binding specificities to various forms of HLA-G and other MHCIs, which may in turn regulate immune suppression.

Structure deposition and release

Deposited: 2006-09-15

Released: 2006-11-07

Revised: 2021-11-10

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: RIIPRHLQL

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 ARG

TYR171

TYR159

THR163

GLU63

PHE33

TYR59

TYR7

GLU62

TRP167

MET5

P2 ILE

TRP97

THR67

TYR7

HIS70

MET45

TYR159

GLU63

ASN66

P3 ILE

GLN155

TRP97

ARG156

HIS70

ASN66

ILE99

TYR159

P4 PRO

ALA69

TYR159

HIS70

ASN66

P5 ARG

ARG65

ALA69

ARG156

HIS70

ASN66

P6 HIS

ARG156

HIS70

PHE22

THR73

SER9

TYR116

ASP74

TRP97

P7 LEU

GLU114

ARG156

ASN77

CYS147

THR73

TRP133

VAL152

LEU124

TYR116

ASP74

P8 GLN

ASN77

LYS146

THR73

P9 LEU

SER143

TYR84

LEU95

THR80

LYS146

TYR123

ASN77

LEU124

TYR116

LEU81

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

ALA159

GLY163

GLU167

ARG171

SER5

GLU59

GLU63

ARG66

ARG7

B Pocket

ILE24

PHE34

ARG45

GLU63

ARG66

ASN67

ARG7

ALA70

PHE9

MET99

C Pocket

ALA70

GLN73

THR74

PHE9

GLN97

D Pocket

TYR114

GLU155

GLN156

ALA159

TYR160

MET99

E Pocket

TYR114

LYS147

ASN152

GLN156

GLN97

F Pocket

GLN116

ASP123

ILE143

ARG146

LYS147

MET77

GLN80

THR81

GLY84

THR95

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-G01:01 IPD-IMGT/HLA* [ipd-imgt:HLA34359]	10 20 30 40 50 60 MGSHSMRYFSAAVSRPGRGEPRFIAMGYVDDTQFVRFDSDSASPRMEPRAPWVEQEGPEY 70 80 90 100 110 120 WEEETRNTKAHAQTDRMNLQTLRGYYNQSEASSHTLQWMIGCDLGSDGRLLRGYEQYAYD 130 140 150 160 170 180 GKDYLALNEDLRSWTAADTAAQISKRKCEAANVAEQRRAYLEGTCVEWLHRYLENGKEML 190 200 210 220 230 240 QRADPPKTHVTHHPVFDYEATLRCWALGFYPAEIILTWQRDGEDQTQDVELVETRPAGDG 250 260 270 TFQKWAAVVVPSGEEQRYTCHVQHEGLPEPLMLRWKQ

3. LIR-2 LIR-2	10 20 30 40 50 60 GTIPKPTLWAEPDSVITQGSPVTLSCQGSLEAQEYRLYREKKSASWITRIRPELVKNGQF 70 80 90 100 110 120 RIPSITWEHTGRYGCQYYSRARWSELSDPLVLVMTGAYPKPTLSAQPSPVVTSGGRVTLQ 130 140 150 160 170 180 CESQVAFGGFILCKEGEDEHPQCLNSQPHARGSSRAIFSVGPVSPNRRWSHRCYGYDLNS 190 PYVWSSPSDLLELLVP

4. Peptide	RIIPRHLQL

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]

2DYP assembly 1

Components

MHC Class I alpha chain [cif]

2DYP assembly 1

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

2DYP assembly 1

Peptide only [cif]

2DYP assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/2dyp

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.