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7WJ2

HLA-C*14:02 binding "LYNTVATL" at 1.28Å 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']
2. Class I alpha
HLA-C*14:02
['A']
3. Peptide
LYNTVATL
['C']

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: 2022-01-05
Released: 2022-06-22
Revised: 2022-07-13

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: LYNTVATL

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

TYR7
TYR171
TYR159
THR163
GLU63
PHE33
TRP167
LYS66
MET5
TYR59
P2 TYR

SER9
LYS66
TRP97
GLN70
PHE22
TYR7
TYR159
PHE99
ALA24
GLU63
TYR67
P3 ASN

TYR159
TRP97
GLN70
LYS66
PHE99
P4 THR

TRP97
GLN70
THR73
LYS66
ARG69
P5 VAL

TRP97
GLN70
THR73
ARG156
GLU152
P6 ALA

SER77
GLU152
TRP147
THR73
ARG156
P7 THR

THR143
ASN80
THR73
TRP147
SER77
LYS146
VAL76
P8 LEU

ASN80
TRP147
TYR123
LEU81
SER77
SER116
LYS146
TYR84
LEU95
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
GLU167
ARG171
SER5
GLU59
ARG63
GLN66
ARG7
B Pocket

ILE24
PHE34
ARG45
ARG63
GLN66
LYS67
ARG7
ARG70
PHE9
MET99
C Pocket

ARG70
GLN73
THR74
PHE9
GLN97
D Pocket

TYR114
GLU155
GLN156
ALA159
TYR160
MET99
E Pocket

TYR114
LYS147
ARG152
GLN156
GLN97
F Pocket

GLN116
ASP123
ILE143
ARG146
LYS147
VAL77
ARG80
ASN81
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
AIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD
        70        80        90
WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-C*14:02
IPD-IMGT/HLA
[ipd-imgt:HLA31091]
        10        20        30        40        50        60
AGSHSMRYFSTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRGEPRAPWVEQEGPEY
        70        80        90       100       110       120
WDRETQKYKRQAQTDRVSLRNLRGYYNQSEAGSHTLQWMFGCDLGPDGRLLRGYDQSAYD
       130       140       150       160       170       180
GKDYIALNEDLRSWTAADTAAQITQRKWEAAREAEQRRAYLEGTCVEWLRRYLENGKETL
       190       200       210       220       230       240
QRAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDG
       250       260       270
TFQKWAAVVVPSGEEQRYTCHVQHEGLPEPLTLRWEP

3. Peptide
LYNTVATL


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]
  1. 7WJ2 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 7WJ2 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 7WJ2 assembly 1  
Peptide only [cif]
  1. 7WJ2 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/7wj2

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