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5DEF

HLA-B*27:247 binding "RRKWRRWHL" at 1.60Å 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-B*27:247
['A']
3. Peptide
RRKWRRWHL
['C']

Species


Locus / Allele group


Publication

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: 2020-04-22

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: RRKWRRWHL

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
GLU63
TRP167
MET5
TYR171
TYR159
TYR59
ARG62
TYR7
P2 ARG

CYS67
HIS9
TYR159
ARG62
GLY26
TYR99
THR24
TYR7
VAL25
ILE66
GLU163
GLU63
VAL34
GLU45
P3 LYS

ILE66
TYR99
TYR159
ARG62
GLN155
LEU156
HIS114
P4 TRP

ARG62
GLN65
ILE66
P5 ARG

GLN155
LEU156
GLU152
P6 ARG

GLN155
ALA69
GLU152
LYS70
ILE66
THR73
P7 TRP

THR73
ALA150
LYS146
GLU152
TRP147
P8 HIS

THR73
GLU76
SER77
THR143
LYS146
TRP147
P9 LEU

LEU81
ILE142
SER77
THR80
ASP116
LEU95
LYS146
TYR84
TRP147
THR143
TYR123
ILE124

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
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

HIS114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

HIS114
TRP147
GLU152
LEU156
ASN97
F Pocket

ASP116
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.

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-B*27:247
IPD-IMGT/HLA
[ipd-imgt:HLA31685]
        10        20        30        40        50        60
GSHSMRYFHTSVSRPGRGEPRFITVGYVDDTLFVRFDSDAASPREEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DRETQICKAKAQTDRESLRTLLRYYNQSEAGSHTLQNMYGCDVGPDGRLLRGYHQDAYDG
       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

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Complete structures

Aligned structures [cif]
  1. 5DEF assembly 1  

Components

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

Derived data

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

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.
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Footnotes