1TMC

HLA-A*68:01 binding "EVAPPEYHRK" at 2.30Å 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
HLA-A*68:01

['A']

3. Peptide
EVAPPEYHRK

['C']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-A / HLA-A*68

Publication

The three-dimensional structure of a class I major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain.

Collins EJ, Garboczi DN, Karpusas MN, Wiley DC

Proc. Natl. Acad. Sci. U.S.A. (1995) 92, 1218-21 [doi:10.1073/pnas.92.4.1218] [pubmed:7862664]

Class I major histocompatibility complex (MHC) molecules are ternary complexes of the soluble serum protein beta 2-microglobulin, MHC heavy chain, and bound peptide. The first two domains (alpha 1, alpha 2) of the heavy chain create the peptide binding cleft and the surface that contacts the T-cell receptor. The third domain (alpha 3) associates with the T-cell co-receptor, CD8, during T-cell recognition. Here we describe the x-ray crystal structure of a human class I MHC molecule, HLA-Aw68, from which the alpha 3 domain has been proteolytically removed. The resulting molecule shows no gross morphological changes compared to the intact protein. A decameric peptide complexed with the intact HLA-Aw68 is seen to bind to the proteolized molecule in the conventional manner, demonstrating that the alpha 3 domain is not required for the structural integrity of the molecule or for peptide binding.

Structure deposition and release

Deposited: 1994-12-19

Released: 1995-03-31

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: Decamer (10 amino acids)

Sequence: EVAPPEYHRK

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

TYR171

TYR159

ARG62

TYR59

TYR7

THR163

ASN63

TRP167

PHE33

MET5

P10 LYS

LEU81

TYR123

ARG114

ASP77

LYS146

THR80

ILE124

ASP116

TYR84

TRP147

THR143

ILE95

P2 VAL

TYR159

TYR9

TYR7

ASN66

ASN63

VAL67

TYR99

MET45

P3 ALA

TYR159

TRP156

TYR99

TYR9

ASN66

P4 PRO

TRP156

ASN66

GLN70

TYR159

P5 PRO

ASN66

ALA69

GLN70

P6 GLU

GLN70

THR73

TRP156

TRP147

GLN155

VAL152

P7 TYR

THR73

P8 HIS

GLN155

TRP147

ALA150

THR73

VAL152

P9 ARG

ASP77

LYS146

TRP147

THR143

VAL76

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

THR163

TRP167

TYR171

MET5

TYR59

ASN63

ASN66

TYR7

B Pocket

ALA24

VAL34

MET45

ASN63

ASN66

VAL67

TYR7

GLN70

TYR9

TYR99

C Pocket

GLN70

THR73

ASP74

TYR9

MET97

D Pocket

ARG114

GLN155

TRP156

TYR159

LEU160

TYR99

E Pocket

ARG114

TRP147

VAL152

TRP156

MET97

F Pocket

ASP116

TYR123

THR143

LYS146

TRP147

ASP77

THR80

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 MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-A68:01 IPD-IMGT/HLA* [ipd-imgt:HLA34091]	10 20 30 40 50 60 GSHSMRYFYTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRNTRNVKAQSQTDRVDLGTLRGYYNQSEAGSHTIQMMYGCDVGSDGRFLRGYRQDAYDG 130 140 150 160 170 KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQWRAYLEGTCVEWLRRYLENG

3. Peptide	EVAPPEYHRK

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]

1TMC assembly 1

Components

MHC Class I alpha chain [cif]

1TMC assembly 1

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

1TMC assembly 1

Peptide only [cif]

1TMC assembly 1

Derived data

Data for this page [json]

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

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.