4WDI

H2-Kd binding "LYLVCGERG" at 2.31Å 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.

Complex type

Class i with peptide

1. Beta 2 microglobulin

['B', 'E']

2. Class I alpha
H2-Kd

['A', 'D']

3. Peptide
LYLVCGERG

['C', 'F']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-K / H2-Kd

Publication

Distortion of the MHC class I binding groove to accommodate an insulin-derived 10-mer peptide.

Motozono C, Pearson JA, De Leenheer E, Rizkallah PJ, Beck K, Trimby A, Sewell AK, Wong FS, Cole DK

J. Biol. Chem. (2015) [doi:10.1074/jbc.m114.622522] [pubmed:26085090]

The non-obese diabetic mouse model of type 1 diabetes continues to be an important tool for delineating the role of T-cell-mediated destruction of pancreatic β-cells. However, little is known about the molecular mechanisms that enable this disease pathway. We show that insulin reactivity by a CD8(+) T-cell clone, known to induce type 1 diabetes, is characterized by weak T-cell antigen receptor binding to a relatively unstable peptide-MHC. The structure of the native 9- and 10-mer insulin epitopes demonstrated that peptide residues 7 and 8 form a prominent solvent-exposed bulge that could potentially be the main focus of T-cell receptor binding. The C terminus of the peptide governed peptide-MHC stability. Unexpectedly, we further demonstrate a novel mode of flexible peptide presentation in which the MHC peptide-binding groove is able to "open the back door" to accommodate extra C-terminal peptide residues.

Structure deposition and release

Deposited: 2014-09-08

Released: 2015-06-24

Revised: 2015-07-01

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: LYLVCGERG

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

GLU62

TYR171

TYR159

TYR59

TYR7

ARG66

PHE99

GLU163

TRP167

GLN63

LEU5

P2 TYR

VAL9

ALA24

PHE22

GLN63

ALA67

PHE45

ARG97

PHE74

ASP70

TYR159

TYR7

ARG66

PHE99

P3 LEU

ASP70

GLU163

PHE99

TYR155

ARG97

TYR159

ARG66

TYR156

P4 VAL

ARG66

ALA67

TYR155

ARG97

SER69

TYR156

ASP70

P5 CYS

ARG97

PHE74

TYR156

PHE116

HIS114

TRP73

ASP70

P6 GLY

TYR155

TYR156

TRP73

ASP152

P7 GLU

LYS146

TYR156

TRP73

ASP152

TRP147

ALA150

P8 ARG

THR143

SER69

TRP73

VAL76

TRP147

SER77

GLN72

LYS146

P9 GLY

THR80

TYR84

TRP147

LYS146

THR143

TRP73

TYR123

ILE142

SER77

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

GLU63

GLN66

ARG7

B Pocket

ILE24

PHE34

ARG45

GLU63

GLN66

ARG67

ARG7

SER70

PHE9

MET99

C Pocket

SER70

GLN73

TRP74

PHE9

GLN97

D Pocket

TYR114

GLU155

TYR156

ALA159

TYR160

MET99

E Pocket

TYR114

LYS147

GLY152

TYR156

GLN97

F Pocket

GLN116

ASP123

ILE143

ARG146

LYS147

VAL77

ARG80

THR81

ARG84

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 MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha H2-Kd	10 20 30 40 50 60 MGPHSLRYFVTAVSRPGLGEPRFIAVGYVDDTQFVRFDSDADNPRFEPRAPWMEQEGPEY 70 80 90 100 110 120 WEEQTQRAKSDEQWFRVSLRTAQRYYNQSKGGSHTFQRMFGCDVGSDWRLLRGYHQFAYD 130 140 150 160 170 180 GRDYIALNEDLKTWTAADTAALITRRKWEQAGDAEYYRAYLEGECVEWLRRYLELGNETL 190 200 210 220 230 240 LRTDSPKAHVTYHPRSQVDVTLRCWALGFYPADITLTWQLNGEDLTQDMELVETRPAGDG 250 260 270 TFQKWAAVVVPLGKEQNYTCHVHHKGLPEPLTLRWKP

3. Peptide	LYLVCGERG

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]

Components

MHC Class I alpha chain [cif]

MHC Class I antigen binding domain (alpha1/alpha2) [cif]

Peptide only [cif]

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/4wdi

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.