7QNG

H2-Db with erp57 and Tapasin at 2.70Å 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 erp57 and tapasin

1. Beta 2 microglobulin

['D']

2. Class I alpha
H2-Db

['C']

3. Erp57, Protein disulfide-isomerase A3

['B']

4. Tapasin

['A']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-D / H2-Db

Publication

Structure of an MHC I-tapasin-ERp57 editing complex defines chaperone promiscuity.

Müller IK, Winter C, Thomas C, Spaapen RM, Trowitzsch S, Tampé R

Nat Commun (2022) 13, 5383 [doi:10.1038/s41467-022-32841-9] [pubmed:36104323]

Adaptive immunity depends on cell surface presentation of antigenic peptides by major histocompatibility complex class I (MHC I) molecules and on stringent ER quality control in the secretory pathway. The chaperone tapasin in conjunction with the oxidoreductase ERp57 is crucial for MHC I assembly and for shaping the epitope repertoire for high immunogenicity. However, how the tapasin-ERp57 complex engages MHC I clients has not yet been determined at atomic detail. Here, we present the 2.7-Å crystal structure of a tapasin-ERp57 heterodimer in complex with peptide-receptive MHC I. Our study unveils molecular details of client recognition by the multichaperone complex and highlights elements indispensable for peptide proofreading. The structure of this transient ER quality control complex provides the mechanistic basis for the selector function of tapasin and showcases how the numerous MHC I allomorphs are chaperoned during peptide loading and editing.

Structure deposition and release

Deposited: 2021-12-20

Released: 2022-09-28

Revised: 2022-09-28

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

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 MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

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 TFQKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWEP

3. Erp57, Protein disulfide-isomerase A3 Erp57, Protein disulfide-isomerase A3	10 20 30 40 50 60 MRLRRLALFPGVALLLAAARLAAASDVLELTDDNFESRISDTGSAGLMLVEFFAPWCGHA 70 80 90 100 110 120 KRLAPEYEAAATRLKGIVPLAKVDCTANTNTCNKYGVSGYPTLKIFRDGEEAGAYDGPRT 130 140 150 160 170 180 ADGIVSHLKKQAGPASVPLRTEEEFKKFISDKDASIVGFFDDSFSEAHSEFLKAASNLRD 190 200 210 220 230 240 NYRFAHTNVESLVNEYDDNGEGIILFRPSHLTNKFEDKTVAYTEQKMTSGKIKKFIQENI 250 260 270 280 290 300 FGICPHMTEDNKDLIQGKDLLIAYYDVDYEKNAKGSNYWRNRVMMVAKKFLDAGHKLNFA 310 320 330 340 350 360 VASRKTFSHELSDFGLESTAGEIPVVAIRTAKGEKFVMQEEFSRDGKALERFLQDYFDGN 370 380 390 400 410 420 LKRYLKSEPIPESNDGPVKVVVAENFDEIVNNENKDVLIEFYAPWCGHCKNLEPKYKELG 430 440 450 460 470 480 EKLSKDPNIVIAKMDATANDVPSPYEVRGFPTIYFSPANKKLNPKKYEGGRELSDFISYL 490 500 QREATNPPVIQEEKPKKKKKAQEDL

4. Tapasin Tapasin	10 20 30 40 50 60 MKSLSLLLAVALGLATAVSAGPAVIECWFVEDASGKGLAKRPGALLLRQGPGEPPPRPDL 70 80 90 100 110 120 DPELYLSVHDPAGALQAAFRRYPRGAPAPHCEMSRFVPLPASAKWASGLTPAQNCPRALD 130 140 150 160 170 180 GAWLMVSISSPVLSLSSLLRPQPEPQQEPVLITMATVVLTVLTHTPAPRVRLGQDALLDL 190 200 210 220 230 240 SFAYMPPTSEAASSLAPGPPPFGLEWRRQHLGKGHLLLAATPGLNGQMPAAQEGAVAFAA 250 260 270 280 290 300 WDDDEPWGPWTGNGTFWLPRVQPFQEGTYLATIHLPYLQGQVTLELAVYKPPKVSLMPAT 310 320 330 340 350 360 LARAAPGEAPPELLCLVSHFYPSGGLEVEWELRGGPGGRSQKAEGQRWLSALRHHSDGSV 370 380 390 400 410 SLSGHLQPPPVTTEQHGARYACRIHHPSLPASGRSAEVTLEGSENLYFQGHHHHHHGSE

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]

7QNG assembly 1

Components

MHC Class I alpha chain [cif]

7QNG assembly 1

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

7QNG assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/7qng

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.