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5VVP

HLA-B*57:03 binding "LSSPVTKSW" at 2.00Å 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*57:03
['A']
3. Peptide
LSSPVTKSW
['C']

Species


Locus / Allele group


Publication

HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome.

Illing PT, Pymm P, Croft NP, Hilton HG, Jojic V, Han AS, Mendoza JL, Mifsud NA, Dudek NL, McCluskey J, Parham P, Rossjohn J, Vivian JP, Purcell AW
Nat Commun (2018) 9, 4693 [doi:10.1038/s41467-018-07109-w]  [pubmed:30410026

Immunophenotypic differences between closely related human leukocyte antigen (HLA) alleles have been associated with divergent clinical outcomes in infection, autoimmunity, transplantation and drug hypersensitivity. Here we explore the impact of micropolymorphism on peptide antigen presentation by three closely related HLA molecules, HLA-B*57:01, HLA-B*57:03 and HLA-B*58:01, that are differentially associated with the HIV elite controller phenotype and adverse drug reactions. For each allotype, we mine HLA ligand data sets derived from the same parental cell proteome to define qualitative differences in peptide presentation using classical peptide binding motifs and an unbiased statistical approach. The peptide repertoires show marked qualitative overlap, with 982 peptides presented by all allomorphs. However, differences in peptide abundance, HLA-peptide stability, and HLA-bound conformation demonstrate that HLA micropolymorphism impacts more than simply the range of peptide ligands. These differences provide grounds for distinct immune reactivity and insights into the capacity of micropolymorphism to diversify immune outcomes.

Structure deposition and release

Deposited: 2017-05-19
Released: 2018-10-03
Revised: 2019-04-17

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: LSSPVTKSW

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

TYR159
TYR59
LEU163
TRP167
PHE33
MET5
TYR171
TYR7
GLU63
P2 SER

MET45
TYR99
GLU63
ASN66
MET67
TYR159
TYR9
TYR7
P3 SER

TYR159
SER70
TYR9
TYR99
LEU156
ASN66
P4 PRO

ASN66
LEU163
TYR159
P5 VAL

TYR116
LEU156
GLN155
VAL152
TYR159
P6 THR

THR73
SER70
TYR9
TYR74
P7 LYS

ASN77
VAL152
GLN155
THR73
TRP147
P8 SER

GLU76
LYS146
ILE80
THR73
TRP147
ASN77
P9 TRP

TYR118
TYR123
ALA117
ILE80
TYR84
ILE95
LYS146
THR143
ALA81
ILE142
ASN77
TYR74
TYR116
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
LEU163
TRP167
TYR171
MET5
TYR59
GLU63
ASN66
TYR7
B Pocket

ALA24
VAL34
MET45
GLU63
ASN66
MET67
TYR7
SER70
TYR9
TYR99
C Pocket

SER70
THR73
TYR74
TYR9
VAL97
D Pocket

ASN114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

ASN114
TRP147
VAL152
LEU156
VAL97
F Pocket

TYR116
TYR123
THR143
LYS146
TRP147
ASN77
ILE80
ALA81
TYR84
ILE95

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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-B*57:03
IPD-IMGT/HLA
[ipd-imgt:HLA25915]
        10        20        30        40        50        60
GSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRMAPRAPWIEQEGPEYW
        70        80        90       100       110       120
DGETRNMKASAQTYRENLRIALRYYNQSEAGSHIIQVMYGCDVGPDGRLLRGHNQYAYDG
       130       140       150       160       170       180
KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide
LSSPVTKSW


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. 5VVP assembly 1  

Components

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

Derived data

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

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