7JI2

H2-Kb binding "SIIQFEHL" at 1.95Å 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', 'E']

2. Class I alpha
H2-Kb

['A', 'D']

3. Peptide
SIIQFEHL

['C', 'F']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-K / H2-Kb

Publication

Pre-T cell receptors topologically sample self-ligands during thymocyte ��-selection.

Li X, Mizsei R, Tan K, Mallis RJ, Duke-Cohan JS, Akitsu A, Tetteh PW, Dubey A, Hwang W, Wagner G, Lang MJ, Arthanari H, Wang JH, Reinherz EL

Science (2020) [doi:10.1126/science.abe0918] [pubmed:33335016]

Self-discrimination, a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre-T cell receptors (preTCRs) and αβTCRs. Using x-ray crystallography, we show how a preTCR applies the concave β-sheet surface of its single variable domain (Vβ) to "horizontally" grab the protruding MHC α2-helix. By contrast, αβTCRs purpose all six complementarity-determining region (CDR) loops of their paired VαVβ module to recognize peptides bound to major histocompatibility complex molecules (pMHCs) in "vertical" head-to-head binding. The preTCR topological fit ensures that CDR3β reaches the peptide's featured C-terminal segment for pMHC sampling, establishing the subsequent αβTCR canonical docking mode. "Horizontal" docking precludes germline CDR1β- and CDR2β-MHC binding to broaden β-chain repertoire diversification before αβTCR-mediated selection refinement. Thus, one subunit successively attunes the recognition logic of related multicomponent receptors.

Structure deposition and release

Deposited: 2020-07-22

Released: 2020-12-23

Revised: 2021-01-20

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Octamer (8 amino acids)

Sequence: SIIQFEHL

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 SER

TYR171

LEU5

TYR59

TRP167

GLU63

TYR159

TYR7

ARG62

LYS66

P2 ILE

ASN70

TYR159

TYR7

LYS66

VAL9

GLU24

GLU63

TYR45

P3 ILE

SER99

GLN114

ARG155

ASN70

TYR159

LEU156

LYS66

P4 GLN

ARG155

ASN70

LYS66

P5 PHE

SER99

GLN114

ARG155

PHE74

VAL97

TYR116

ASN70

SER73

VAL9

GLU24

TYR22

P6 GLU

TYR116

TRP147

SER73

ASP77

GLU152

ALA150

ARG155

P7 HIS

VAL76

SER73

TRP147

ASP77

LYS146

P8 LEU

TYR123

ASP77

THR80

TYR84

TRP147

ILE142

THR143

LYS146

TYR116

LEU81

ILE95

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

ALA159

GLY163

GLU167

ARG171

SER5

GLU59

ARG63

GLN66

ARG7

B Pocket

MET24

PHE34

ARG45

ARG63

GLN66

LYS67

ARG7

GLY70

PHE9

ILE99

C Pocket

GLY70

GLN73

SER74

PHE9

GLN97

D Pocket

TYR114

GLU155

ARG156

ALA159

TYR160

ILE99

E Pocket

TYR114

LYS147

GLY152

ARG156

GLN97

F Pocket

GLN116

ASP123

ILE143

HIS146

LYS147

VAL77

ARG80

THR81

GLY84

THR95

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-Kb	10 20 30 40 50 60 MGPHSLRYFVTAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWMEQEGPEY 70 80 90 100 110 120 WERETQKAKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQQYAYD 130 140 150 160 170 180 GCDYIALNEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRYLKNGNATL 190 200 210 220 230 240 LRTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLTWQLNGEELIQDMELVETRPAGDG 250 260 270 280 TFQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPPST

3. Peptide	SIIQFEHL

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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or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.

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]

Components

MHC Class I alpha chain [cif]

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

Peptide only [cif]

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/7ji2

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.