1BZ9

H2-Db binding "FAPGVFPYM" at 2.80Å 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

1. Beta 2 microglobulin

['B']

2. Class I alpha
H2-Db

['A']

3. Peptide
FAPGVFPYM

['C']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-D / H2-Db

Publication

Structural evidence of T cell xeno-reactivity in the absence of molecular mimicry.

Zhao R, Loftus DJ, Appella E, Collins EJ

J. Exp. Med. (1999) 189, 359-70 [doi:10.1084/jem.189.2.359] [pubmed:9892618]

The T cell receptor (TCR), from a xeno-reactive murine cytotoxic T lymphocyte clone AHIII12.2, recognizes murine H-2Db complexed with peptide p1027 (FAPGVFPYM), as well as human HLA-A2.1 complexed with peptide p1049 (ALWGFFPVL). A commonly proposed model (the molecular mimicry model) used to explain TCR cross-reactivity suggests that the molecular surfaces of the recognized complexes are similar in shape, charge, or both, in spite of the primary sequence differences. To examine the mechanism of xeno-reactivity of AHIII12.2, we have determined the crystal structures of A2/p1049 and Db/p1027 to 2.5 A and 2.8 A resolution, respectively. The crystal structures show that the TCR footprint regions of the two class I complexes are significantly different in shape and charge. We propose that rather than simple molecular mimicry, unpredictable arrays of common and differential contacts on the two class I complexes are used for their recognition by the same TCR.

Structure deposition and release

Deposited: 1998-11-06

Released: 1999-05-24

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: FAPGVFPYM

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 PHE

PHE33

MET5

ARG62

LYS66

GLU163

TRP167

GLU63

TYR171

TYR159

TYR59

TYR7

P2 ALA

GLU63

TYR159

TYR7

TYR45

LYS66

P3 PRO

LYS66

SER99

TYR159

GLU9

TYR156

TYR7

GLN70

P4 GLY

TYR156

GLN70

LYS66

P6 PHE

TRP73

TRP133

TRP147

TYR156

ALA152

ALA153

PHE116

LEU114

P7 PRO

SER150

TRP73

TRP147

ALA152

P8 TYR

VAL76

TRP147

TRP73

THR143

LYS146

SER77

ASN80

GLN72

P9 MET

LEU95

SER77

TRP73

TYR123

THR143

LYS146

PHE116

TRP147

ILE142

TYR84

LEU81

ASN80

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

ARG5

TRP59

THR63

ALA66

PHE7

B Pocket

VAL24

ARG34

GLU45

THR63

ALA66

LYS67

PHE7

GLU70

THR9

GLY99

C Pocket

GLU70

PHE73

ARG74

THR9

MET97

D Pocket

GLN114

TYR155

LYS156

LEU159

GLU160

GLY99

E Pocket

GLN114

GLU147

ALA152

LYS156

MET97

F Pocket

ALA116

ILE123

ARG143

TRP146

GLU147

LEU77

LEU80

LEU81

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 MIQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKD 70 80 90 WSFYILAHTEFTPTETDTYACRVKHDSMAEPKTVYWDRDM

2. Class I alpha H2-Db	10 20 30 40 50 60 PHSMRYFETAVSRPGLEEPRYISVGYVDNKEFVRFDSDAENPRYEPRAPWMEQEGPEYWE 70 80 90 100 110 120 RETQKAKGQEQWFRVSLRNLLGYYNQSAGGSHTLQQMSGCDLGSDWRLLRGYLQFAYEGR 130 140 150 160 170 180 DYIALNEDLKTWTAADMAAQITRRKWEQSGAAEHYKAYLEGECVEWLHRYLKNGNATLLR 190 200 210 220 230 240 TDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGTF 250 260 270 QKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWERWE

3. Peptide	FAPGVFPYM

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.

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Complete structures

Aligned structures [cif]

1BZ9 assembly 1

Components

MHC Class I alpha chain [cif]

1BZ9 assembly 1

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

1BZ9 assembly 1

Peptide only [cif]

1BZ9 assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/1bz9

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.