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6WZY

H2-Db binding "SGPDNGAVAV" at 1.50Å 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
H2-Db
['A']
3. Peptide
SGPDNGAVAV
['C']

Species


Locus / Allele group


Publication

Overlapping Peptides Elicit Distinct CD8+ T Cell Responses following Influenza A Virus Infection.

Assmus LM, Guan J, Wu T, Farenc C, Sng XYX, Zareie P, Nguyen A, Nguyen AT, Tscharke DC, Thomas PG, Rossjohn J, Gras S, Croft NP, Purcell AW, La Gruta NL
J. Immunol. (2020) [doi:10.4049/jimmunol.2000689]  [pubmed:32868409

The presentation of pathogen-derived peptides on MHC class I molecules is essential for the initiation of adaptive CD8+ T cell immunity, which in turn is critical for effective control of many significant human infections. The identification of immunogenic pathogen-derived epitopes and a detailed understanding of how they are recognized by TCRs is essential for the design of effective T cell-based vaccines. In this study, we have characterized the T cell recognition and immune responses in mice to two naturally presented influenza A virus-derived peptides previously identified from virally infected cells via mass spectrometry. These neuraminidase-derived peptides, NA181-190 (SGPDNGAVAV) and NA181-191 (SGPDNGAVAVL), are completely overlapping with the exception of a 1 aa extension at the C terminus of the longer peptide. This minor peptidic difference results in the induction of two completely independent and non-cross-reactive T cell populations that show distinct functional characteristics after influenza A virus infection of B6 mice. We show that the unique TCR reactivity to the overlapping peptides is present in the naive repertoire prior to immune expansion in B6 mice. Moreover, we provide a structural explanation underlying the distinct CD8+ T cell reactivities, which reinforces the concept that peptide length is a key determinant of Ag specificity in CD8+ T cell responses.

Structure deposition and release

Deposited: 2020-05-14
Released: 2020-09-16
Revised: 2020-10-07

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Decamer (10 amino acids)

Sequence: SGPDNGAVAV

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 SER

MET5
GLU163
GLU63
TYR171
TRP167
TYR159
LYS66
PHE33
TYR59
TYR7
P10 VAL

SER77
TRP147
THR143
TYR84
LEU81
ASN80
LYS146
TYR123
LEU95
TRP73
P2 GLY

TYR159
LYS66
GLU163
GLU63
TYR7
P3 PRO

TYR156
SER99
LEU114
TYR159
LYS66
GLU9
GLN97
GLN70
TYR7
P4 ASP

HIS155
GLN70
LYS66
TYR156
P5 ASN

HIS155
PHE74
TRP73
GLN97
GLN70
PHE116
TYR156
P6 GLY

GLN70
HIS155
TRP73
P7 ALA

TRP73
P8 VAL

SER150
TRP73
TRP147
LYS146
P9 ALA

TRP73
SER77
ASN80
TRP147
VAL76
LYS146

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
GLY70
PHE9
MET99
C Pocket

GLY70
GLN73
TRP74
PHE9
GLN97
D Pocket

TYR114
GLU155
HIS156
ALA159
TYR160
MET99
E Pocket

TYR114
LYS147
GLY152
HIS156
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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
H2-Db
        10        20        30        40        50        60
MGPHSMRYFETAVSRPGLEEPRYISVGYVDNKEFVRFDSDAENPRYEPRAPWMEQEGPEY
        70        80        90       100       110       120
WERETQKAKGQEQWFRVSLRNLLGYYNQSAGGSHTLQQMSGCDLGSDWRLLRGYLQFAYE
       130       140       150       160       170       180
GRDYIALNEDLKTWTAADMAAQITRRKWEQSGAAEHYKAYLEGECVEWLHRYLKNGNATL
       190       200       210       220       230       240
LRTDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDG
       250       260       270
TFQKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWEPPP

3. Peptide
SGPDNGAVAV


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. 6WZY assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 6WZY assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 6WZY assembly 1  
Peptide only [cif]
  1. 6WZY assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/6wzy

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