H2-Kb binding "SIINFEKL" with Ly49c NK receptor at 2.90Å resolution
Data provenance
Information sections
- Publication
- Peptide details
- Peptide neighbours
- Binding cleft pockets
- Chain sequences
- Downloadable data
- Data license
- Footnotes
Complex type
Class i with peptide and ly49c
H2-Kb
SIINFEKL
Species
Locus / Allele group
Molecular architecture of the major histocompatibility complex class I-binding site of Ly49 natural killer cell receptors.
Natural killer (NK) cells play a vital role in the detection and destruction of virally infected and tumor cells during innate immune responses. The highly polymorphic Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex class I (MHC-I) molecules on target cells. Despite the determination of two Ly49-MHC-I complex structures, the molecular features of Ly49 receptors that confer specificity for particular MHC-I alleles have not been identified. To understand the functional architecture of Ly49-binding sites, we determined the crystal structures of Ly49C and Ly49G and completed refinement of the Ly49C-H-2K(b) complex. This information, combined with mutational analysis of Ly49A, permitted a structure-based classification of Ly49s that we used to dissect the binding site into three distinct regions, each having different roles in MHC recognition. One region, located at the center of the binding site, has a similar structure across the Ly49 family and mediates conserved interactions with MHC-I that contribute most to binding. However, the preference of individual Ly49s for particular MHC-I molecules is governed by two regions that flank the central region and are structurally more variable. One of the flanking regions divides Ly49s into those that recognize both H-2D and H-2K versus only H-2D ligands, whereas the other discriminates among H-2D or H-2K alleles. The modular design of Ly49-binding sites provides a framework for predicting the MHC-binding specificity of Ly49s that have not been characterized experimentally.
Structure deposition and release
Data provenance
Publication data retrieved from PDBe REST API8 and PMCe REST API9
Other structures from this publication
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
SER
LEU5
LYS66
TRP167
GLU63
TYR171
ARG62
TYR159
TYR59
TYR7
|
P2
ILE
VAL9
GLU63
ASN70
TYR7
SER99
GLU24
TYR45
LYS66
TYR159
|
P3
ILE
GLN114
ASN70
TYR159
LEU156
ARG155
SER99
LYS66
|
P4
ASN
ASN70
ARG155
LYS66
|
P5
PHE
ARG155
PHE74
VAL9
VAL97
ASN70
GLU24
TYR22
SER73
SER99
TYR116
GLN114
|
P6
GLU
TRP147
ALA150
SER73
ASP77
TYR116
GLU152
ARG155
|
P7
LYS
SER73
TRP147
ASP77
GLN72
LYS146
VAL76
|
P8
LEU
THR80
TYR116
LEU81
TRP147
ASP77
TYR84
LYS146
ILE95
THR143
TYR123
|
Colour key
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]
A Pocket
TYR159
THR163
TRP167
TYR171
LEU5
TYR59
GLU63
LYS66
TYR7
|
B Pocket
GLU24
VAL34
TYR45
GLU63
LYS66
ALA67
TYR7
ASN70
VAL9
SER99
|
C Pocket
ASN70
SER73
PHE74
VAL9
VAL97
|
D Pocket
GLN114
ARG155
LEU156
TYR159
LEU160
SER99
|
E Pocket
GLN114
TRP147
GLU152
LEU156
VAL97
|
F Pocket
TYR116
TYR123
THR143
LYS146
TRP147
ASP77
THR80
LEU81
TYR84
ILE95
|
Colour key
Data provenance
1. Beta 2 microglobulin
Beta 2 microglobulin
|
10 20 30 40 50 60
IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDW 70 80 90 SFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDM |
2. Class I alpha
H2-Kb
|
10 20 30 40 50 60
GPHSLRYFVTAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWMEQEGPEYW 70 80 90 100 110 120 ERETQKAKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQQYAYDG 130 140 150 160 170 180 CDYIALNEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRYLKNGNATLL 190 200 210 220 230 240 RTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLTWQLNGEELIQDMELVETRPAGDGT 250 260 270 FQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRW |
3. Natural Killer Cell Receptor Ly49c
Natural Killer Cell Receptor Ly49c
|
10 20 30 40 50 60
RGVKYWFCYSTKCYYFIMNKTTWSGCKANCQHYGVPILKIEDEDELKFLQRHVIPGNYWI 70 80 90 100 110 120 GLSYDKKKKEWAWIDNGPSKLDMKIKKMNFKSRGCVFLSKARIEDIDCNIPYYCICGKKL DKFPD |
4. Peptide
|
SIINFEKL
|
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
Components
Data license
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.