HLA-A*24:02 binding "RYGFVANF" at 1.89Å resolution
Data provenance
Information sections
- Publication
- Peptide details
- Peptide neighbours
- Binding cleft pockets
- Chain sequences
- Downloadable data
- Data license
- Footnotes
Complex type
HLA-A*24:02
RYGFVANF
Species
Locus / Allele group
Crystal structures of N-myristoylated lipopeptide-bound HLA class I complexes indicate reorganization of B-pocket architecture upon ligand binding.
Rhesus monkeys have evolved MHC-encoded class I allomorphs such as Mamu-B∗098 that are capable of binding N-myristoylated short lipopeptides rather than conventional long peptides; however, it remains unknown whether such antigen-binding molecules exist in other species, including humans. We herein demonstrate that human leukocyte antigen (HLA)-A∗24:02 and HLA-C∗14:02 proteins, which are known to bind conventional long peptides, also have the potential to bind N-myristoylated short lipopeptides. These HLA class I molecules shared a serine at position 9 (Ser9) with Mamu-B∗098, in contrast to most MHC class I molecules that harbor a larger amino acid residue, such as tyrosine, at this position. High resolution X-ray crystallographic analyses of lipopeptide-bound HLA-A∗24:02 and HLA-C∗14:02 complexes indicated that Ser9 was at the bottom of the B pocket with its small hydroxymethyl side chain directed away from the B-pocket cavity, thereby contributing to the formation of a deep hydrophobic cavity suitable for accommodating the long-chain fatty acid moiety of lipopeptide ligands. Upon peptide binding, however, we found the hydrogen-bond network involving Ser9 was reorganized, and the remodeled B pocket was able to capture the second amino acid residue (P2) of peptide ligands. Apart from the B pocket, virtually no marked alterations were observed for the A and F pockets upon peptide and lipopeptide binding. Thus, we concluded that the structural flexibility of the large B pocket of HLA-A∗2402 and HLA-C∗1402 primarily accounted for their previously unrecognized capacity to bind such chemically distinct ligands as conventional peptides and N-myristoylated lipopeptides.
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
ARG
MET5
TYR171
TYR159
TYR59
GLU62
THR163
TYR7
LYS66
GLY167
PHE33
PHE99
ARG170
GLU63
|
P2
TYR
HIS70
GLU63
LYS66
PHE99
ALA24
VAL67
TYR159
PHE22
SER9
THR163
MET45
TYR7
|
P3
GLY
TYR159
PHE99
LYS66
|
P4
PHE
HIS114
PHE99
GLN156
TYR159
GLN155
|
P5
VAL
HIS70
ASN77
HIS114
GLN156
ASP74
MET97
TYR116
THR73
|
P6
ALA
TYR116
THR73
ASN77
TRP147
VAL152
|
P7
ASN
GLU76
LYS146
THR73
TRP147
ILE80
ASN77
THR143
|
P8
PHE
TYR116
TYR84
TYR123
LYS146
ALA81
LEU95
TRP147
ILE80
ILE142
ASN77
THR143
|
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
ALA159
GLY163
ASP167
ARG171
SER5
GLU59
GLU63
GLY66
ARG7
|
B Pocket
ILE24
PHE34
ARG45
GLU63
GLY66
LYS67
ARG7
ALA70
PHE9
MET99
|
C Pocket
ALA70
GLN73
THR74
PHE9
GLN97
|
D Pocket
TYR114
GLU155
GLN156
ALA159
TYR160
MET99
|
E Pocket
TYR114
LYS147
HIS152
GLN156
GLN97
|
F Pocket
GLN116
ASP123
ILE143
ARG146
LYS147
GLU77
ARG80
ILE81
ARG84
THR95
|
Colour key
Data provenance
1. Beta 2 microglobulin
Beta 2 microglobulin
|
10 20 30 40 50 60
AIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM |
2. Class I alpha
HLA-A*24:02
IPD-IMGT/HLA
[ipd-imgt:HLA34790] |
10 20 30 40 50 60
AGSHSMRYFSTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEY 70 80 90 100 110 120 WDEETGKVKAHSQTDRENLRIALRYYNQSEAGSHTLQMMFGCDVGSDGRFLRGYHQYAYD 130 140 150 160 170 180 GKDYIALKEDLRSWTAADMAAQITKRKWEAAHVAEQQRAYLEGTCVDGLRRYLENGKETL 190 200 210 220 230 240 QRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDG 250 260 270 TFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP |
3. Peptide
|
RYGFVANF
|
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.