5WER

H2-Dd with peptide editor TAPBPR at 3.41Å 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 tapbpr

1. Beta 2 microglobulin

['B', 'E', 'H', 'K']

2. Class I alpha
H2-Dd

['A', 'D', 'G', 'J']

3. TAPBPR (Tapasin homologue)

['C', 'F', 'I', 'L']

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: 2019-08-28

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Binding cleft pockets

Peptide sidechain binding pockets (static)

Peptide terminii and backbone binding residues (static)

A Pocket

TYR159

GLU163

TRP167

TYR171

LEU5

TYR59

GLU63

ARG66

TYR7

B Pocket

GLU24

VAL34

TYR45

GLU63

ARG66

ALA67

TYR7

ASN70

VAL9

ALA99

C Pocket

ASN70

CYS73

PHE74

VAL9

TRP97

D Pocket

TRP114

ARG155

ASP156

TYR159

LEU160

ALA99

E Pocket

TRP114

TRP147

ALA152

ASP156

TRP97

F Pocket

PHE116

TYR123

THR143

LYS146

TRP147

ASP77

THR80

ALA81

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 H2-Dd	10 20 30 40 50 60 MSHSLRYFVTAVSRPGFGEPRYMEVGYVDNTEFVRFDSDAENPRYEPRARWIEQEGPEYW 70 80 90 100 110 120 ERETRRAKGNEQCFRVDLRTALRYYNQSAGGSHTLQWMAGCDVESDGRLLRGYWQFAYDG 130 140 150 160 170 180 CDYIALNEDLKTWTAADMAAQITRRKWEQAGAAERDRAYLEGECVEWLRRYLKNGNATLL 190 200 210 220 230 240 RTDPPKAHVTHHRRPEGDVTLRCWALGFYPADITLTWQLNGEELTQEMELVETRPAGDGT 250 260 270 FQKWASVVVPLGKEQKYTCHVEHEGLPEPLTLRWGKE

3. TAPBPR (Tapasin homologue) TAPBPR (Tapasin homologue)	10 20 30 40 50 60 KPHPAEGQWRAVDVVLDCFLVKDGAHRGALASSEDRARASLVLKQVPVLDDGSLEDFTDF 70 80 90 100 110 120 QGGTLAQDDPPIIFEASVDLVQIPQAEALLHADCSGKEVTCEISRYFLQMTETTVKTAAW 130 140 150 160 170 180 FMANVQVSGGGPSISLVMKTPRVAKNEVLWHPTLNLPLSPQGTVRTAVEFQVMTQTQSLS 190 200 210 220 230 240 FLLGSSASLDCGFSMAPGLDLISVEWRLQHKGRGQLVYSWTAGQGQAVRKGATLEPAQLG 250 260 270 280 290 300 MARDASLTLPGLTIQDEGTYICQITTSLYRAQQIIQLNIQASPKVRLSLANEALLPTLIC 310 320 330 340 350 360 DIAGYYPLDVVVTWTREELGGSPAQVSGASFSSLRQSVAGTYSISSSLTAEPGSAGATYT 370 380 390 CQVTHISLEEPLGASTQVVPPERRLEGGLEVLFQ

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

Data can be downloaded to your local machine from the links below.

Clicking on the clipboard icon will copy the url for the data to your clipboard.

This can then be used to load the structure/data directly from the url into an application like PyMol (for 3D structures) using the load command:

e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif

or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.

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]

Derived data

Data for this page [json]

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

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.