5WES

H2-Dd binding "RGPGC" at 2.71Å 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']

2. Class I alpha
H2-Dd

['A']

3. Peptide
RGPGC

['P']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-D / H2-Dd

Publication

Crystal structure of a TAPBPR-MHC-I complex reveals the mechanism of peptide editing in antigen presentation.

Jiang J, Natarajan K, Boyd LF, Morozov GI, Mage MG, Margulies DH

Science (2017) [doi:10.1126/science.aao5154] [pubmed:29025991]

Central to CD8⁺ T cell-mediated immunity is the recognition of peptide-major histocompatibility complex class I (p-MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein-related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.

Structure deposition and release

Deposited: 2017-07-10

Released: 2017-10-18

Revised: 2017-12-13

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Pentamer (5 amino acids)

Sequence: RGPGC

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

LEU5

ARG62

GLU63

TRP167

TYR159

TYR59

TYR171

GLU163

TYR7

CYS164

ARG66

P2 GLY

ARG66

GLU163

GLU63

TYR159

TYR7

P3 PRO

TRP97

TYR7

ASN70

ALA99

TRP114

ARG66

TYR159

P4 GLY

ASN70

ARG155

ARG66

TRP114

TRP97

P5 CYS

GLY69

CYS73

ASN70

PHE116

TRP114

ARG155

PHE74

TRP97

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

LEU159

CYS163

LEU167

LEU171

ARG5

TRP59

THR63

ALA66

PHE7

B Pocket

VAL24

ARG34

GLU45

THR63

ALA66

LYS67

PHE7

GLU70

THR9

GLY99

C Pocket

GLU70

PHE73

ARG74

THR9

MET97

D Pocket

GLN114

ASP155

ARG156

LEU159

GLU160

GLY99

E Pocket

GLN114

GLU147

ALA152

ARG156

MET97

F Pocket

ALA116

ILE123

ARG143

TRP146

GLU147

LEU77

ALA80

LEU81

TYR84

GLN95

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 IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDW 70 80 90 SFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDM

2. Class I alpha H2-Dd	10 20 30 40 50 60 SHSLRYFVTAVSRPGFGEPRYMEVGYVDNTEFVRFDSDAENPRYEPRARWIEQEGPEYWE 70 80 90 100 110 120 RETRRAKGNEQCFRVDLRTALRYYNQSAGGSHTLQWMAGCDVESDGRLLRGYWQFAYDGC 130 140 150 160 170 180 DYIALNEDLKTWTAADMAAQITRRKWEQAGAAERDRAYLEGECVEWLRRYLKNGNATLLR 190 200 210 220 230 240 TDPPKAHVTHHRRPEGDVTLRCWALGFYPADITLTWQLNGEELTQEMELVETRPAGDGTF 250 260 270 QKWASVVVPLGKEQKYTCHVEHEGLPEPLTLRWGKE

3. Peptide	RGPGC

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]

5WES assembly 1

Components

MHC Class I alpha chain [cif]

5WES assembly 1

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

5WES assembly 1

Peptide only [cif]

5WES assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/5wes

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.