5OPI

H2-Db with peptide editor TAPBPR at 3.30Å 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']

2. Class I alpha
H2-Db

['A']

3. TAPBPR (Tapasin homologue)

['C']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-D / H2-Db

Publication

Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading and editing.

Thomas C, Tampé R

Science (2017) [doi:10.1126/science.aao6001] [pubmed:29025996]

Adaptive immunity is shaped by a selection of peptides presented on major histocompatibility complex class I (MHC I) molecules. The chaperones Tapasin (Tsn) and TAP-binding protein-related (TAPBPR) facilitate MHC I peptide loading and high-affinity epitope selection. Despite the pivotal role of Tsn and TAPBPR in controlling the hierarchical immune response, their catalytic mechanism remains unknown. Here, we present the x-ray structure of the TAPBPR-MHC I complex, which delineates the central step of catalysis. TAPBPR functions as peptide selector by remodeling the MHC I α2-1-helix region, stabilizing the empty binding groove, and inserting a loop into the groove that interferes with peptide binding. The complex explains how mutations in MHC I-specific chaperones cause defects in antigen processing and suggests a unifying mechanism of peptide proofreading.

Structure deposition and release

Deposited: 2017-08-09

Released: 2017-10-18

Revised: 2017-12-06

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

MET5

TYR59

GLU63

LYS66

TYR7

B Pocket

SER24

VAL34

TYR45

GLU63

LYS66

ALA67

TYR7

GLN70

GLU9

SER99

C Pocket

GLN70

TRP73

PHE74

GLU9

GLN97

D Pocket

LEU114

HIS155

TYR156

TYR159

LEU160

SER99

E Pocket

LEU114

TRP147

ALA152

TYR156

GLN97

F Pocket

PHE116

TYR123

THR143

LYS146

TRP147

SER77

ASN80

LEU81

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 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW 70 80 90 SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha H2-Db	10 20 30 40 50 60 GPHSMRYFETAVSRPGLEEPRYISVGYVDNKEFVRFDSDAENPRYEPRAPWMEQEGPEYW 70 80 90 100 110 120 ERETQKAKGQEQWFRVSLRNLLGYYNQSAGGSHTLQQMSGCDLGSDWRLLRGYLQFAYEG 130 140 150 160 170 180 RDYIALNEDLKTWTAADMAAQITRRKWEQSGAAEHYKAYLEGECVEWLHRYLKNGNATLL 190 200 210 220 230 240 RTDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGT 250 260 270 FQKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWEPSSA

3. TAPBPR (Tapasin homologue) TAPBPR (Tapasin homologue)	10 20 30 40 50 60 ADPGVDVVLDCFLVKDGAHRGALASSEDRARASLVLKQVPVLDDGSLEDFTDFQGGTLAQ 70 80 90 100 110 120 DDPPIIFEASVDLVQIPQAEALLHADASGKEVTCEISRYFLQMTETTVKTAAWFMANVQV 130 140 150 160 170 180 SGGGPSISLVMKTPRVAKNEVLWHPTLNLPLSPQGTVRTAVEFQVMTQTQSLSFLLGSSA 190 200 210 220 230 240 SLDCGFSMAPGLDLISVEWRLQHKGRGQLVYSWTAGQGQAVRKGATLEPAQLGMARDASL 250 260 270 280 290 300 TLPGLTIQDEGTYICQITTSLYRAQQIIQLNIQASPKVRLSLANEALLPTLICDIAGYYP 310 320 330 340 350 360 LDVVVTWTREELGGSPAQVSGASFSSLRQSVAGTYSISSSLTAEPGSAGATYTCQVTHIS 370 LEEPLGASTQVVP

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]

5OPI assembly 1

Components

MHC Class I alpha chain [cif]

5OPI assembly 1

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

5OPI assembly 1

Derived data

Data for this page [json]

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

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.