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7WT4

HLA-A*24:02 binding "RYGFVANF" at 1.89Å 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.

Information sections


Complex type

Class i with peptide

1. Beta 2 microglobulin
['B', 'E']
2. Class I alpha
HLA-A*24:02
['A', 'D']
3. Peptide
RYGFVANF
['C', 'F']

Species


Locus / Allele group


Publication

Crystal structures of N-myristoylated lipopeptide-bound HLA class I complexes indicate reorganization of B-pocket architecture upon ligand binding.

Asa, M., Morita, D., Kuroha, J., Mizutani, T., Mori, N., Mikami, B., Sugita, M.
(2022) 298, 102100-102100 [doi:10.1016/j.jbc.2022.102100]  [pubmed:35667438

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

Deposited: 2022-02-03
Released: 2022-06-22
Revised: 2022-07-06

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Octamer (8 amino acids)

Sequence: RYGFVANF

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

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

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
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

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
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

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Please take note of the data license. Using data from this site assumes that you have read and will comply with the license.

Complete structures

Aligned structures [cif]
  1. 7WT4 assembly 1  
  2. 7WT4 assembly 2  

Components

MHC Class I alpha chain [cif]
  1. 7WT4 assembly 1  
  2. 7WT4 assembly 2  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 7WT4 assembly 1  
  2. 7WT4 assembly 2  
Peptide only [cif]
  1. 7WT4 assembly 1  
  2. 7WT4 assembly 2  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/7wt4

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