H2-Db with erp57 and Tapasin at 2.70Å resolution
Data provenance
Information sections
Complex type
Class i with erp57 and tapasin
H2-Db
Species
Locus / Allele group
Structure of an MHC I-tapasin-ERp57 editing complex defines chaperone promiscuity.
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
Data provenance
Publication data retrieved from PDBe REST API8 and PMCe REST API9
Other structures from this publication
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
Data provenance
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
Components
Data license
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.