2AK4

HLA-B*35:08 presenting "LPEPLPQGQLTAY" to Alpha/Beta T cell receptor at 2.50Å 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', 'R']

2. Class I alpha
HLA-B*35:08

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

3. Peptide
LPEPLPQGQLTAY

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

4. T cell receptor alpha
TRAV19

['D']

5. T cell receptor beta
TRBV6

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*35

Publication

T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide.

Tynan FE, Burrows SR, Buckle AM, Clements CS, Borg NA, Miles JJ, Beddoe T, Whisstock JC, Wilce MC, Silins SL, Burrows JM, Kjer-Nielsen L, Kostenko L, Purcell AW, McCluskey J, Rossjohn J

Nat. Immunol. (2005) 6, 1114-22 [doi:10.1038/ni1257] [pubmed:16186824]

Unusually long major histocompatibility complex (MHC) class I-restricted epitopes are important in immunity, but their 'bulged' conformation represents a potential obstacle to alphabeta T cell receptor (TCR)-MHC class I docking. To elucidate how such recognition is achieved while still preserving MHC restriction, we have determined here the structure of a TCR in complex with HLA-B(*)3508 presenting a peptide 13 amino acids in length. This complex was atypical of TCR-peptide-MHC class I interactions, being dominated at the interface by peptide-mediated interactions. The TCR assumed two distinct orientations, swiveling on top of the centrally bulged, rigid peptide such that only limited contacts were made with MHC class I. Although the TCR-peptide recognition resembled an antibody-antigen interaction, the TCR-MHC class I contacts defined a minimal 'generic footprint' of MHC-restriction. Thus our findings simultaneously demonstrate the considerable adaptability of the TCR and the 'shape' of MHC restriction.

Structure deposition and release

Deposited: 2005-08-03

Released: 2005-10-11

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: Tridecamer (13 amino acids)

Sequence: LPEPLPQGQLTAY

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 LEU

MET5

ARG62

TRP167

TYR159

TYR59

ASN63

PHE33

LEU163

TYR7

ILE66

TYR171

P10 LEU

ASN70

THR69

THR73

P11 THR

LYS146

VAL152

ALA150

THR73

TRP147

P12 ALA

LYS146

SER77

ASN80

TRP147

GLU76

THR73

P13 TYR

ILE95

ILE124

TYR74

ARG97

TYR123

ASN80

LEU81

LYS146

SER77

GLN96

SER116

THR143

TYR84

TRP147

P2 PRO

ILE66

TYR99

TYR159

ASN63

PHE67

TYR9

TYR7

P3 GLU

TYR9

TYR99

TYR159

ASN70

ILE66

ARG156

GLN155

ARG97

P4 PRO

LEU163

ARG62

ILE66

TYR159

P5 LEU

GLN65

ASN70

THR69

ILE66

P6 PRO

GLN155

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

ARG156

TYR159

LEU160

TYR99

E Pocket

ASP114

TRP147

VAL152

ARG156

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 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW 70 80 90 SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-B35:08 IPD-IMGT/HLA* [ipd-imgt:HLA31926]	10 20 30 40 50 60 GSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRNTQIFKTNTQTYRESLRNLRGYYNQSEAGSHIIQRMYGCDLGPDGRLLRGHDQSAYDG 130 140 150 160 170 180 KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQRRAYLEGLCVEWLRRYLENGKETLQ 190 200 210 220 230 240 RADPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide	LPEPLPQGQLTAY

4. T cell receptor alpha T cell receptor alpha TRAV19	10 20 30 40 50 60 HMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLFWYKQPPSGELVFLIRRNSFDEQN 70 80 90 100 110 120 EISGRYSWNFQKSTSSFNFTITASQVVDSAVYFCALSGFYNTDKLIFGTGTRLQVFPNIQ 130 140 150 160 170 180 NPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAV 190 200 210 AWSNKSDFACANAFNNSIIPEDTFFPSPESS

5. T cell receptor beta T cell receptor beta TRBV6	10 20 30 40 50 60 HMNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWYRQDPGMGLRLIYYSASEGTTDKG 70 80 90 100 110 120 EVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCASPGLAGEYEQYFGPGTRLTVTEDLKN 130 140 150 160 170 180 VFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKE 190 200 210 220 230 240 QPALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEA WGRAD

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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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]

2AK4 assembly 1

Components

MHC Class I alpha chain [cif]

2AK4 assembly 1

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

2AK4 assembly 1

Peptide only [cif]

2AK4 assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/2ak4

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.