2ESV

HLA-E*01:01 presenting "VMAPRTLIL" to Alpha/Beta T cell receptor at 2.60Å 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-E*01:01

['A']

3. Peptide
VMAPRTLIL

['P']

4. T cell receptor alpha
TRAV26

['D']

5. T cell receptor beta
TRBV14

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-E / HLA-E*01

Publication

Structural basis for a major histocompatibility complex class Ib-restricted T cell response.

Hoare HL, Sullivan LC, Pietra G, Clements CS, Lee EJ, Ely LK, Beddoe T, Falco M, Kjer-Nielsen L, Reid HH, McCluskey J, Moretta L, Rossjohn J, Brooks AG

Nat. Immunol. (2006) 7, 256-64 [doi:10.1038/ni1312] [pubmed:16474394]

In contrast to antigen-specific immunity orchestrated by major histocompatibility complex (MHC) class Ia molecules, the ancestrally related nonclassical MHC class Ib molecules generally mediate innate immune responses. Here we have demonstrated the structural basis by which the MHC class Ib molecule HLA-E mediates an adaptive MHC-restricted cytotoxic T lymphocyte response to human cytomegalovirus. Highly constrained by host genetics, the response showed notable fine specificity for position 8 of the viral peptide, which is the sole discriminator of self versus nonself. Despite the evolutionary divergence of MHC class Ia and class Ib molecules, the structure of the T cell receptor-MHC class Ib complex was very similar to that of conventional T cell receptor-MHC class Ia complexes. These results emphasize the evolutionary 'ambiguity' of HLA-E, which not only interacts with innate immune receptors but also has the functional capacity to mediate virus-specific cytotoxic T lymphocyte responses during adaptive immunity.

Structure deposition and release

Deposited: 2005-10-27

Released: 2006-03-21

Revised: 2011-07-13

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Nonamer (9 amino acids)

Sequence: VMAPRTLIL

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 VAL

GLU63

LEU5

ARG62

TYR171

TRP167

HIS99

TYR159

TYR59

THR163

TYR7

P2 MET

TYR159

TYR7

THR70

SER24

SER66

GLU63

ALA67

HIS9

TRP97

MET45

HIS99

P3 ALA

TRP97

HIS99

TYR159

THR70

GLN156

SER66

P4 PRO

SER66

TYR159

P5 ARG

TRP97

GLU152

GLN156

HIS155

P6 THR

PHE116

GLU152

GLN156

THR70

PHE74

TRP97

ILE73

P7 LEU

ILE73

SER147

GLU152

ASN77

PHE116

TRP133

LEU124

P8 ILE

LYS146

VAL76

ILE73

ASN77

P9 LEU

THR80

PHE116

TYR84

ASN77

SER143

LEU95

TYR123

LYS146

LEU124

LEU81

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

LEU159

CYS163

LEU167

LEU171

LYS5

TRP59

THR63

ALA66

PHE7

B Pocket

VAL24

ARG34

VAL45

THR63

ALA66

ARG67

PHE7

ALA70

THR9

GLY99

C Pocket

ALA70

PHE73

ARG74

THR9

MET97

D Pocket

GLN114

GLN155

ARG156

LEU159

GLU160

GLY99

E Pocket

GLN114

ASN147

ALA152

ARG156

MET97

F Pocket

ALA116

LEU123

GLU143

SER146

ASN147

LEU77

LEU80

ARG81

TYR84

GLN95

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-E01:01 IPD-IMGT/HLA* [ipd-imgt:HLA34073]	10 20 30 40 50 60 SHSLKYFHTSVSRPGRGEPRFISVGYVDDTQFVRFDNDAASPRMVPRAPWMEQEGSEYWD 70 80 90 100 110 120 RETRSARDTAQIFRVNLRTLRGYYNQSEAGSHTLQWMHGCELGPDRRFLRGYEQFAYDGK 130 140 150 160 170 180 DYLTLNEDLRSWTAVDTAAQISEQKSNDASEAEHQRAYLEDTCVEWLHKYLEKGKETLLH 190 200 210 220 230 240 LEPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQQDGEGHTQDTELVETRPAGDGTF 250 260 270 QKWAAVVVPSGEEQRYTCHVQHEGLPEPVTLRWKP

3. Peptide	VMAPRTLIL

4. T cell receptor alpha T cell receptor alpha TRAV26	10 20 30 40 50 60 KTTQPPSMDCAEGRAANLPCNHSTISGNEYVYWYRQIHSQGPQYIIHGLKNNETNEMASL 70 80 90 100 110 120 IITEDRKSSTLILPHATLRDTAVYYCIVVRSSNTGKLIFGQGTTLQVKPDIQNPDPAVYQ 130 140 150 160 170 180 LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDF 190 ACANAFNNSIIPEDTFFPS

5. T cell receptor beta T cell receptor beta TRBV14	10 20 30 40 50 60 GVTQFPSHSVIEKGQTVTLRCDPISGHDNLYWYRRVMGKEIKFLLHFVKESKQDESGMPN 70 80 90 100 110 120 NRFLAERTGGTYSTLKVQPAELEDSGVYFCASSQDRDTQYFGPGTRLTVLEDLKNVFPPE 130 140 150 160 170 180 VAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALN 190 200 210 220 230 DSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRAD

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]

2ESV assembly 1

Components

MHC Class I alpha chain [cif]

2ESV assembly 1

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

2ESV assembly 1

Peptide only [cif]

2ESV assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/2esv

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.