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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.

Information sections


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']

Species


Locus / Allele group


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-B*44:05
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

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Complete structures

Aligned structures [cif]
  1. 3DXA assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 3DXA assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 3DXA assembly 1  
Peptide only [cif]
  1. 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