5DEG
HLA-B*27:06 binding "RRKWRRWHL" at 1.83Å 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
- Publication
- Peptide details
- Peptide neighbours
- Binding cleft pockets
- Chain sequences
- Downloadable data
- Data license
- Footnotes
Complex type
1. Beta 2 microglobulin
['B']
2. Class I alpha
HLA-B*27:06
HLA-B*27:06
['A']
3. Peptide
RRKWRRWHL
RRKWRRWHL
['C']
Species
Locus / Allele group
Increased conformational flexibility characterizes HLA-B*27 subtypes associated with ankylosing spondylitis.
Loll B, Fabian H, Huser H, Hee CS, Ziegler A, Uchanska-Ziegler B, Ziegler A
(2016)
[doi:10.1002/art.39567]
[pubmed:26748477]
Objective
Dissimilarities in antigen processing and presentation are known to contribute to the differential association of HLA-B*27 subtypes with the inflammatory rheumatic disease ankylosing spondylitis (AS). In support of this notion, previous x-ray crystallographic data showed that peptides can be displayed by almost identical HLA-B*27 molecules in a subtype-dependent manner, allowing cytotoxic T lymphocytes to distinguish between these subtypes. For example, a human self-peptide derived from vasoactive intestinal peptide receptor type 1 (pVIPR; sequence RRKWRRWHL) is displayed in a single conformation by B*27:09 (which is not associated with AS), while B*27:05 (which is associated with AS) presents the peptide in a dual binding mode. In addition, differences in conformational flexibility between these subtypes might affect their stability or antigen presentation capability. This study was undertaken to investigate B*27:04 and B*27:06, another pair of minimally distinct HLA-B*27 subtypes, to assess whether dual peptide conformations or structural dynamics play a role in the initiation of AS.Methods
Using x-ray crystallography, we determined the structures of the pVIPR-B*27:04 and pVIPR-B*27:06 complexes and used isotope-edited infrared (IR) spectroscopy to probe the dynamics of these HLA-B*27 subtypes.Results
As opposed to B*27:05 and B*27:09, B*27:04 (which is associated with AS) displays pVIPR conventionally and B*27:06 (which is not associated with AS) presents the peptide in a dual conformation. Comparison of the 4 HLA-B*27 subtypes using IR spectroscopy revealed that B*27:04 and B*27:05 possess elevated molecular dynamics compared to the nonassociated subtypes B*27:06 and B*27:09.Conclusion
Our results demonstrate that an increase in conformational flexibility characterizes the disease-associated subtypes B*27:04 and B*27:05.Structure deposition and release
Deposited: 2015-08-25
Released: 2015-11-18
Revised: 2019-12-18
Data provenance
Publication data retrieved from PDBe REST API8 and PMCe REST API9
Other structures from this publication
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
GLU163
ARG62
GLU63
TYR7
TYR171
MET5
TYR59
TYR159
TRP167
|
P2
ARG
TYR159
GLU163
ARG62
ILE66
VAL25
GLY26
GLU45
VAL34
TYR7
HIS9
GLU63
CYS67
TYR99
THR24
|
P3
LYS
ASP114
TYR116
TYR159
TYR99
ILE66
LEU156
|
P4
TRP
ARG62
ILE66
GLN65
|
P5
ARG
GLU152
GLN155
|
P6
ARG
GLU152
LYS70
ILE66
HIS9
TYR99
TYR116
|
P7
TRP
GLU152
ALA150
SER77
TYR116
TRP147
|
P8
HIS
THR80
SER77
TRP147
LYS146
THR73
GLU76
|
P9
LEU
TYR84
LEU95
SER77
THR80
THR143
LYS146
TYR123
LEU81
ILE124
TRP147
TYR116
|
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]
Peptide sidechain binding pockets (static)
Peptide terminii and backbone binding residues (static)
|
A Pocket
TYR159
GLU163
TRP167
TYR171
MET5
TYR59
GLU63
ILE66
TYR7
|
B Pocket
THR24
VAL34
GLU45
GLU63
ILE66
CYS67
TYR7
LYS70
HIS9
TYR99
|
C Pocket
LYS70
THR73
ASP74
HIS9
ASN97
|
D Pocket
ASP114
GLN155
LEU156
TYR159
LEU160
TYR99
|
E Pocket
ASP114
TRP147
GLU152
LEU156
ASN97
|
F Pocket
TYR116
TYR123
THR143
LYS146
TRP147
SER77
THR80
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.
|
1. Beta 2 microglobulin
Beta 2 microglobulin
|
10 20 30 40 50 60
MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM |
|
2. Class I alpha
HLA-B*27:06
IPD-IMGT/HLA
[ipd-imgt:HLA33851] |
10 20 30 40 50 60
GSHSMRYFHTSVSRPGRGEPRFITVGYVDDTLFVRFDSDAASPREEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRETQICKAKAQTDRESLRTLLRYYNQSEAGSHTLQNMYGCDVGPDGRLLRGYDQYAYDG 130 140 150 160 170 180 KDYIALNEDLSSWTAADTAAQITQRKWEAAREAEQLRAYLEGECVEWLRRYLENGKETLQ 190 200 210 220 230 240 RADPPKTHVTHHPISDHEATLRCWALGFYPGEITLTWQRDGEDQTQDTELVETRPAGDRT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP |
|
3. Peptide
|
RRKWRRWHL
|
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
Data can be downloaded to your local machine from the links below.
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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.
Components
MHC Class I alpha chain [cif]
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
Peptide only [cif]
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
- 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.