3MV8

HLA-B*35:01 presenting "HPVGEADYFEY" 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
HLA-B*35:01

['A']

3. Peptide
HPVGEADYFEY

['C']

4. T cell receptor alpha
TRAV20

['D']

5. T cell receptor beta
TRBV9

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*35

Publication

Allelic polymorphism in the T cell receptor and its impact on immune responses.

Gras S, Chen Z, Miles JJ, Liu YC, Bell MJ, Sullivan LC, Kjer-Nielsen L, Brennan RM, Burrows JM, Neller MA, Khanna R, Purcell AW, Brooks AG, McCluskey J, Rossjohn J, Burrows SR

J. Exp. Med. (2010) 207, 1555-67 [doi:10.1084/jem.20100603] [pubmed:20566715]

In comparison to human leukocyte antigen (HLA) polymorphism, the impact of allelic sequence variation within T cell receptor (TCR) loci is much less understood. Particular TCR loci have been associated with autoimmunity, but the molecular basis for this phenomenon is undefined. We examined the T cell response to an HLA-B*3501-restricted epitope (HPVGEADYFEY) from Epstein-Barr virus (EBV), which is frequently dominated by a TRBV9*01(+) public TCR (TK3). However, the common allelic variant TRBV9*02, which differs by a single amino acid near the CDR2beta loop (Gln55-->His55), was never used in this response. The structure of the TK3 TCR, its allelic variant, and a nonnaturally occurring mutant (Gln55-->Ala55) in complex with HLA-B*3501(HPVGEADYFEY) revealed that the Gln55-->His55 polymorphism affected the charge complementarity at the TCR-peptide-MHC interface, resulting in reduced functional recognition of the cognate and naturally occurring variants of this EBV peptide. Thus, polymorphism in the TCR loci may contribute toward variability in immune responses and the outcome of infection.

Structure deposition and release

Deposited: 2010-05-03

Released: 2010-06-09

Revised: 2011-07-20

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Undecamer (11 amino acids)

Sequence: HPVGEADYFEY

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 HIS

MET5

TYR59

LEU163

ARG62

TYR7

TRP167

PHE33

TYR171

TYR159

ILE66

ASN63

P10 GLU

THR143

SER77

ASN80

LYS146

THR73

GLU76

TRP147

P11 TYR

LEU81

ILE95

GLN96

ARG97

TYR74

TRP147

TYR84

THR143

TYR123

SER77

ILE124

ASN80

LYS146

SER116

ILE142

P2 PRO

PHE67

TYR7

ILE66

TYR99

LEU163

ASN63

TYR9

TYR159

P3 VAL

TYR9

TYR159

ILE66

LEU156

TYR99

P4 GLY

ILE66

P5 GLU

TYR9

ARG97

TYR74

ASN70

THR73

P6 ALA

GLN155

P7 ASP

ALA150

P8 TYR

TRP147

LYS146

ALA150

P9 PHE

GLN155

ALA150

TRP147

VAL152

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

LEU163

TRP167

TYR171

MET5

TYR59

ASN63

ILE66

TYR7

B Pocket

ALA24

VAL34

THR45

ASN63

ILE66

PHE67

TYR7

ASN70

TYR9

TYR99

C Pocket

ASN70

THR73

TYR74

TYR9

ARG97

D Pocket

ASP114

GLN155

LEU156

TYR159

LEU160

TYR99

E Pocket

ASP114

TRP147

VAL152

LEU156

ARG97

F Pocket

SER116

TYR123

THR143

LYS146

TRP147

SER77

ASN80

LEU81

TYR84

ILE95

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 HLA-B35:01 IPD-IMGT/HLA* [ipd-imgt:HLA34423]	10 20 30 40 50 60 GSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRNTQIFKTNTQTYRESLRNLRGYYNQSEAGSHIIQRMYGCDLGPDGRLLRGHDQSAYDG 130 140 150 160 170 180 KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQ 190 200 210 220 230 240 RADPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide	HPVGEADYFEY

4. T cell receptor alpha T cell receptor alpha TRAV20	10 20 30 40 50 60 QVTQSPEALRLQEGESSSLNCSYTVSGLRGLFWYRQDPGKGPEFLFTLYSAGEEKEKERL 70 80 90 100 110 120 KATLTKKESFLHITAPKPEDSATYLCAVQDLGTSGSRLTFGEGTQLTVNPNIQNPDPAVY 130 140 150 160 170 180 QLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSD 190 FACANAFNNSIIPEDTFFPS

5. T cell receptor beta T cell receptor beta TRBV9	10 20 30 40 50 60 MDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQGLQFLIHYYNGEERAKGN 70 80 90 100 110 120 ILERFSAQQFPDLHSELNLSSLELGDSALYFCASSARSGELFFGEGSRLTVLEDLKNVFP 130 140 150 160 170 180 PEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPA 190 200 210 220 230 240 LNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR AD

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]

3MV8 assembly 1

Components

MHC Class I alpha chain [cif]

3MV8 assembly 1

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

3MV8 assembly 1

Peptide only [cif]

3MV8 assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/3mv8

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.