3KPR

HLA-B*44:05 presenting "EEYLKAWTF" 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', 'G']

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

['A', 'F']

3. Peptide
EEYLKAWTF

['C', 'H']

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

T cell allorecognition via molecular mimicry.

Macdonald WA, Chen Z, Gras S, Archbold JK, Tynan FE, Clements CS, Bharadwaj M, Kjer-Nielsen L, Saunders PM, Wilce MC, Crawford F, Stadinsky B, Jackson D, Brooks AG, Purcell AW, Kappler JW, Burrows SR, Rossjohn J, McCluskey J

Immunity (2009) 31, 897-908 [doi:10.1016/j.immuni.2009.09.025] [pubmed:20064448]

T cells often alloreact with foreign human leukocyte antigens (HLA). Here we showed the LC13 T cell receptor (TCR), selected for recognition on self-HLA-B( *)0801 bound to a viral peptide, alloreacts with B44 allotypes (HLA-B( *)4402 and HLA-B( *)4405) bound to two different allopeptides. Despite extensive polymorphism between HLA-B( *)0801, HLA-B( *)4402, and HLA-B( *)4405 and the disparate sequences of the viral and allopeptides, the LC13 TCR engaged these peptide-HLA (pHLA) complexes identically, accommodating mimicry of the viral peptide by the allopeptide. The viral and allopeptides adopted similar conformations only after TCR ligation, revealing an induced-fit mechanism of molecular mimicry. The LC13 T cells did not alloreact against HLA-B( *)4403, and the single residue polymorphism between HLA-B( *)4402 and HLA-B( *)4403 affected the plasticity of the allopeptide, revealing that molecular mimicry was associated with TCR specificity. Accordingly, molecular mimicry that is HLA and peptide dependent is a mechanism for human T cell alloreactivity between disparate cognate and allogeneic pHLA complexes.

Structure deposition and release

Deposited: 2009-11-16

Released: 2009-12-22

Revised: 2017-11-01

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: EEYLKAWTF

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

GLU63

GLU55

TYR171

TYR159

LEU163

ARG170

TYR59

ARG62

MET5

TYR7

SER167

P2 GLU

LYS45

ASN70

GLU63

TYR7

TYR99

THR24

SER67

TYR159

LEU163

TYR9

ILE66

P3 TYR

TYR159

LEU163

ASP114

TYR9

ILE66

TYR99

ASP156

ARG97

GLN155

P4 LEU

ASN70

THR69

GLN155

ILE66

P5 LYS

ASN70

TRP147

ASP114

VAL152

ASP156

ARG97

TRP133

GLN155

TYR116

THR73

P6 ALA

THR73

P7 TRP

TRP147

GLN155

ALA150

THR73

ASN77

VAL152

P8 THR

GLU76

LYS146

THR73

ASN77

TRP147

THR143

P9 PHE

TYR84

THR80

TRP147

ILE95

THR143

ILE142

TYR116

ALA81

TYR123

GLU76

LYS146

ASN77

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	EEYLKAWTF

4. T cell receptor alpha T cell receptor alpha TRAV26	10 20 30 40 50 60 KTTQPNSMESNEEEPVHLPCNHSTISGTDYIHWYRQLPSQGPEYVIHGLTSNVNNRMASL 70 80 90 100 110 120 AIAEDRKSSTLILHRATLRDAAVYYCILPLAGGTSYGKLTFGQGTILTVHPNIQNPDPAV 130 140 150 160 170 180 YQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKS 190 200 DFACANAFNNSIIPEDTFFPS

5. T cell receptor beta T cell receptor beta TRBV7	10 20 30 40 50 60 GVSQSPRYKVAKRGQDVALRCDPISGHVSLFWYQQALGQGPEFLTYFQNEAQLDKSGLPS 70 80 90 100 110 120 DRFFAERPEGSVSTLKIQRTQQEDSAVYLCASSLGQAYEQYFGPGTRLTVTEDLKNVFPP 130 140 150 160 170 180 EVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPAL 190 200 210 220 230 240 NDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRA D

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]

3KPR assembly 1

Components

MHC Class I alpha chain [cif]

3KPR assembly 1

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

3KPR assembly 1

Peptide only [cif]

3KPR assembly 1

Derived data

Data for this page [json]

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

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.

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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.