3DXA

HLA-B*44:05 presenting "EENLLDFVRF" to Alpha/Beta T cell receptor at 3.50Å 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', 'G', 'L']

2. Class I alpha
HLA-B*44:05

['A', 'F', 'K']

3. Peptide
EENLLDFVRF

['C', 'H', 'M']

4. T cell receptor alpha
TRAV26

['D']

5. T cell receptor beta
TRBV7

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*44

Publication

Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.

Archbold JK, Macdonald WA, Gras S, Ely LK, Miles JJ, Bell MJ, Brennan RM, Beddoe T, Wilce MC, Clements CS, Purcell AW, McCluskey J, Burrows SR, Rossjohn J

J. Exp. Med. (2009) 206, 209-19 [doi:10.1084/jem.20082136] [pubmed:19139173]

Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell-mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR-HLA-B*4405(EENLLDFVRF) complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.

Structure deposition and release

Deposited: 2008-07-23

Released: 2009-01-27

Revised: 2021-10-20

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: EENLLDFVRF

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 GLU

LEU163

GLU63

TYR171

SER167

MET5

TYR159

TYR7

ARG170

ARG62

TYR59

P10 PHE

TRP147

ASN77

TYR118

TYR116

THR80

THR143

TYR84

LYS146

TYR123

ILE95

TYR74

ALA81

P2 GLU

SER67

TYR159

TYR7

TYR9

ILE66

LYS45

TYR99

THR24

LEU163

GLU63

P3 ASN

ASP156

GLN155

TYR159

ARG97

TYR9

TYR99

ILE66

P4 LEU

SER67

THR69

ILE66

ASN70

GLN155

P5 LEU

VAL152

GLN155

P6 ASP

THR69

THR73

P7 PHE

ALA150

VAL152

P8 VAL

THR73

TRP147

ASN77

TYR116

VAL152

P9 ARG

TRP147

ASN77

THR143

GLU76

LYS146

THR73

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

SER167

TYR171

MET5

TYR59

GLU63

ILE66

TYR7

B Pocket

THR24

VAL34

LYS45

GLU63

ILE66

SER67

TYR7

ASN70

TYR9

TYR99

C Pocket

ASN70

THR73

TYR74

TYR9

ARG97

D Pocket

ASP114

GLN155

ASP156

TYR159

LEU160

TYR99

E Pocket

ASP114

TRP147

VAL152

ASP156

ARG97

F Pocket

TYR116

TYR123

THR143

LYS146

TRP147

ASN77

THR80

ALA81

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 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW 70 80 90 SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-B44:05 IPD-IMGT/HLA* [ipd-imgt:HLA30859]	10 20 30 40 50 60 GSHSMRYFYTAMSRPGRGEPRFITVGYVDDTLFVRFDSDATSPRKEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRETQISKTNTQTYRENLRTALRYYNQSEAGSHIIQRMYGCDVGPDGRLLRGYDQYAYDG 130 140 150 160 170 180 KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQDRAYLEGLCVESLRRYLENGKETLQ 190 200 210 220 230 240 RADPPKTHVTHHPISDHEVTLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide	EENLLDFVRF

4. T cell receptor alpha T cell receptor alpha TRAV26	10 20 30 40 50 60 AKTTQPTSMDCAEGRAANLPCNHSTISGNEYVYWYRQIHSQGPQYIIHGLKNNETNEMAS 70 80 90 100 110 120 LIITEDRKSSTLILPHATLRDTAVYYCIVWGGYQKVTFGTGTKLQVIPIQNPDPAVYQLR 130 140 150 160 170 180 DSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFAC 190 ANAFNNSIIPEDTFFPSPE

5. T cell receptor beta T cell receptor beta TRBV7	10 20 30 40 50 60 TGVSQNPRHKITKRGQNVTFRCDPISEHNRLYWYRQTLGQGPEFLTYFQNEAQLEKSRLL 70 80 90 100 110 120 SDRFSAERPKGSFSTLEIQRTEQGDSAMYLCASRYRDDSYNEQFFGPGTRLTVLEDLKNV 130 140 150 160 170 180 FPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQ 190 200 210 220 230 240 PALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAW GRAD

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

Data can be downloaded to your local machine from the links below.

Clicking on the clipboard icon will copy the url for the data to your clipboard.

This can then be used to load the structure/data directly from the url into an application like PyMol (for 3D structures) using the load command:

e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif

or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.

Please take note of the data license. Using data from this site assumes that you have read and will comply with the license.

Complete structures

Aligned structures [cif]

3DXA assembly 1

Components

MHC Class I alpha chain [cif]

3DXA assembly 1

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

3DXA assembly 1

Peptide only [cif]

3DXA assembly 1

Derived data

Data for this page [json]

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

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.