5IVX

H2-Dd presenting "RGPGRAFVTI" to Alpha/Beta T cell receptor at 2.10Å 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 and alpha beta tcr

1. Beta 2 microglobulin

['B']

2. Class I alpha
H2-Dd

['A']

3. Peptide
RGPGRAFVTI

['P']

4. T cell receptor alpha
TRAV14

['E']

5. T cell receptor beta
TRBV29

['F']

Information on this structure on STCRdab.

Species

Mus musculus (Mouse)

Locus / Allele group

H2-D / H2-Dd

Publication

An allosteric site in the T-cell receptor C�� domain plays a critical signalling role.

Natarajan K, McShan AC, Jiang J, Kumirov VK, Wang R, Zhao H, Schuck P, Tilahun ME, Boyd LF, Ying J, Bax A, Margulies DH, Sgourakis NG

Nat Commun (2017) 8, 15260 [doi:10.1038/ncomms15260] [pubmed:28508865]

The molecular mechanism through which the interaction of a clonotypic αβ T-cell receptor (TCR) with a peptide-loaded major histocompatibility complex (p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a high-affinity TCR (B4.2.3) to examine the structural changes that accompany binding to its p/MHC ligand (P18-I10/H2-D^d). In addition to conformational changes in complementarity-determining regions (CDRs) of the TCR seen in comparison of unliganded and bound X-ray structures, NMR characterization of the TCR β-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site. Remodelling of electrostatic interactions near the Cβ H3 helix at the membrane-proximal face of the TCR, a region implicated in interactions with the CD3 co-receptor, suggests a possible role for an allosteric mechanism in TCR signalling. The contribution of these TCR residues to signal transduction is supported by mutagenesis and T-cell functional assays.

Structure deposition and release

Deposited: 2016-03-21

Released: 2017-03-29

Revised: 2017-06-21

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Decamer (10 amino acids)

Sequence: RGPGRAFVTI

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

TRP167

TYR171

TYR159

TYR59

GLU63

GLU163

TYR7

ARG66

P10 ILE

ASP77

THR143

TYR84

TYR123

LYS146

ALA81

THR80

TRP147

LEU95

ILE142

P2 GLY

TYR7

ARG66

ARG62

TYR159

GLU63

P3 PRO

TRP97

ALA99

TYR159

TYR7

ASN70

TRP114

ARG66

P4 GLY

ASN70

TRP114

ASP156

ARG66

TRP97

P5 ARG

SER73

TRP147

ASN70

ASP77

PHE74

TRP97

PHE116

P6 ALA

ARG155

SER73

ASN70

P7 PHE

GLY69

GLN72

SER73

P8 VAL

ALA152

ARG155

SER73

TRP147

P9 THR

TRP147

SER73

VAL76

LYS146

ASP77

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

TYR159

GLU163

TRP167

TYR171

LEU5

TYR59

GLU63

ARG66

TYR7

B Pocket

GLU24

VAL34

TYR45

GLU63

ARG66

ALA67

TYR7

ASN70

VAL9

ALA99

C Pocket

ASN70

SER73

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 MIQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKD 70 80 90 WSFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDM

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

3. Peptide	RGPGRAFVTI

4. T cell receptor alpha T cell receptor alpha TRAV14	10 20 30 40 50 60 QQVRQSPQSLTVWEGETAILNCSYENSAFDYFPWYQQFPGEGPALLISILSVSNKKEDGR 70 80 90 100 110 120 FTIFFNKREKKLSLHIADSQPGDSATYFCAASASFGDNSKLIWGLGTSLVVNPNIQNPEP 130 140 150 160 170 180 AVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSN 190 QTSFTCQDIFKETN

5. T cell receptor beta T cell receptor beta TRBV29	10 20 30 40 50 60 MKVTQMPRYLIKRMGENVLLECGQDMSHETMYWYRQDPGLGLQLIYISYDVDSNSEGDIP 70 80 90 100 110 120 KGYRVSRKKREHFSLILDSAKTNQTSVYFCASSLGHTEVFFGKGTRLTVVEDLRNVTPPK 130 140 150 160 170 180 VSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSY 190 200 210 220 230 ALSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGR

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]

5IVX assembly 1

Components

MHC Class I alpha chain [cif]

5IVX assembly 1

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

5IVX assembly 1

Peptide only [cif]

5IVX assembly 1

Derived data

Data for this page [json]

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

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.