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5W67

HLA-C*06:02 binding "VRSRRALRL" at 2.30Å 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*06:02
['A']
3. Peptide
VRSRRALRL
['C']

Species


Locus / Allele group


Publication

The molecular basis for peptide repertoire selection in the Human Leucocyte Antigen (HLA) C*06:02 molecule.

Mobbs JI, Illing PT, Dudek NL, Brooks AG, Baker DG, Purcell AW, Rossjohn J, Vivian JP
J. Biol. Chem. (2017) [doi:10.1074/jbc.M117.806976]  [pubmed:28855257

Human leukocyte antigen (HLA)-C*06:02 is identified as the allele associated with the highest risk for the development of the autoimmune skin disease psoriasis. However, the diversity and mode of peptide presentation by the HLA-C*06:02 molecule remains unclear. Here, we describe the endogenous peptide repertoire of ∼3,000 sequences for HLA-C*06:02 that defines the peptide-binding motif for this HLA allomorph. We found that HLA-C*06:02 predominantly presents nonamer peptides with dominant arginine anchors at the P2 and P7 positions and a preference for small hydrophobic residues at the C terminus (PΩ). To determine the structural basis of this selectivity, we determined crystal structures of HLA-C*06:02 in complex with two self-peptides (ARTELYRSL and ARFNDLRFV) and an analogue of a melanocyte autoantigen (ADAMTSL5, VRSRR-abu-LRL) implicated in psoriasis. These structures revealed that HLA-C*06:02 possesses a deep peptide-binding groove comprising two electronegative B- and E-pockets that coincide with the preference for P2 and P7 arginine anchors. The ADAMTSL5 autoantigen possessed a P7-Leu instead of the P7-Arg residue, but nevertheless was accommodated within the HLA-C*06:02 antigen-binding cleft. Collectively, our results provide the structural basis for understanding peptide repertoire selection in HLA-C*06:02.

Structure deposition and release

Deposited: 2017-06-16
Released: 2017-08-23
Revised: 2017-11-01

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: VRSRRALRL

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 VAL

TYR99
TRP167
PHE33
MET5
GLU63
TYR7
TYR159
TYR59
LYS66
TYR171
THR163
P2 ARG

GLU63
SER24
TYR67
TYR99
TRP97
PHE22
TYR7
GLN70
TYR159
ASP9
LYS66
P3 SER

TRP156
TYR159
LYS66
TYR99
ARG69
P4 ARG

LYS66
ARG69
P5 ARG

GLU152
GLN155
TRP97
GLN70
TRP156
P7 LEU

TRP147
LEU95
TRP97
GLN70
ALA73
ASN77
ASP74
SER116
ASP114
P8 ARG

THR143
LYS80
ALA73
ASN77
TRP147
ARG69
P9 LEU

LEU95
TYR84
LEU81
THR143
TYR123
ASN77
LYS80
LYS146
SER116
TRP147

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

TYR159
THR163
TRP167
TYR171
MET5
TYR59
GLU63
LYS66
TYR7
B Pocket

SER24
VAL34
GLY45
GLU63
LYS66
TYR67
TYR7
GLN70
ASP9
TYR99
C Pocket

GLN70
ALA73
ASP74
ASP9
TRP97
D Pocket

ASP114
GLN155
TRP156
TYR159
LEU160
TYR99
E Pocket

ASP114
TRP147
GLU152
TRP156
TRP97
F Pocket

SER116
TYR123
THR143
LYS146
TRP147
ASN77
LYS80
LEU81
TYR84
LEU95

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-C*06:02
IPD-IMGT/HLA
[ipd-imgt:HLA35196]
        10        20        30        40        50        60
CSHSMRYFDTAVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPRGEPRAPWVEQEGPEYW
        70        80        90       100       110       120
DRETQKYKRQAQADRVNLRKLRGYYNQSEDGSHTLQWMYGCDLGPDGRLLRGYDQSAYDG
       130       140       150       160       170       180
KDYIALNEDLRSWTAADTAAQITQRKWEAAREAEQWRAYLEGTCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPEPLTLRWEP

3. Peptide
VRSRRALRL


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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or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.
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. 5W67 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 5W67 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 5W67 assembly 1  
Peptide only [cif]
  1. 5W67 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/5w67

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