3TFK

Truncated H2-Ld presenting "QLSDVPMDL" to Alpha/Beta T cell receptor at 2.75Å 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

Truncated class i with peptide and alpha beta tcr

1. Class I alpha
H2-Ld

['A']

2. Peptide
QLSDVPMDL

['B']

3. T cell receptor alpha
TRAV9

['C']

4. T cell receptor beta
TRBV13

['D']

Information on this structure on STCRdab.

Species

Mus musculus (Mouse)

Locus / Allele group

H2-L / H2-Ld

Publication

T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex.

Adams JJ, Narayanan S, Liu B, Birnbaum ME, Kruse AC, Bowerman NA, Chen W, Levin AM, Connolly JM, Zhu C, Kranz DM, Garcia KC

Immunity (2011) 35, 681-93 [doi:10.1016/j.immuni.2011.09.013] [pubmed:22101157]

T cell receptor (TCR) engagement of peptide-major histocompatibility complex (pMHC) is essential to adaptive immunity, but it is unknown whether TCR signaling responses are influenced by the binding topology of the TCR-peptide-MHC complex. We developed yeast-displayed pMHC libraries that enabled us to identify new peptide sequences reactive with a single TCR. Structural analysis showed that four peptides bound to the TCR with distinct 3D and 2D affinities using entirely different binding chemistries. Three of the peptides that shared a common docking mode, where key TCR-MHC germline interactions are preserved, induced TCR signaling. The fourth peptide failed to induce signaling and was recognized in a substantially different TCR-MHC binding mode that apparently exceeded geometric tolerances compatible with signaling. We suggest that the stereotypical TCR-MHC docking paradigm evolved from productive signaling geometries and that TCR signaling can be modulated by peptides that are recognized in alternative TCR-pMHC binding orientations.

Structure deposition and release

Deposited: 2011-08-15

Released: 2011-12-07

Revised: 2012-01-18

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: QLSDVPMDL

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 GLN

VAL66

TYR171

TYR159

ARG62

TYR59

ILE63

TRP167

GLU163

P2 LEU

TYR7

ILE63

GLU163

TYR45

TYR159

TYR99

VAL66

P3 SER

TYR99

TYR156

TYR159

ARG97

VAL66

P4 ASP

TYR155

ARG97

GLN70

P5 VAL

TRP73

GLN70

TYR155

GLY69

P6 PRO

TYR155

PHE116

ARG97

TRP73

GLN70

GLU114

P7 MET

TYR155

ALA150

TRP147

GLY151

TRP73

ASN77

LYS146

ALA152

P8 ASP

TRP73

ASN77

LYS146

TRP147

P9 LEU

THR143

PHE116

LEU81

TRP147

TYR123

LEU95

TRP73

ASN77

LYS146

ILE142

TYR84

THR80

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

THR24

PHE34

ARG45

ARG63

GLN66

VAL67

ARG7

GLY70

TYR9

MET99

C Pocket

GLY70

GLN73

TRP74

TYR9

GLN97

D Pocket

TYR114

GLU155

TYR156

ALA159

TYR160

MET99

E Pocket

TYR114

LYS147

GLY152

TYR156

GLN97

F Pocket

GLN116

ASP123

ILE143

ARG146

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. Class I alpha H2-Ld	10 20 30 40 50 60 MGPHSMRYYETATSRRGLGEPRYTSVGYVDDKEFVRFDSDAENPRYEPQVPWMEQEGPEY 70 80 90 100 110 120 WERITQVAKGQEQWFRVNLRTLLGYYNQSAGGTHTLQRMYGCDVGSDGRLLRGYEQFAYD 130 140 150 160 170 GCDYIALNEDLRTWTAADMAAQITRRKWEQAGAAEYYRAYLEGECVEWLHRYLKNGNATL

2. Peptide	QLSDVPMDL

3. T cell receptor alpha T cell receptor alpha TRAV9	10 20 30 40 50 60 GSHMAQSVTQPDARVTVSEGASLQLRCKYSYSATPYLFWYVQYPRQGLQMLLKYYSGDPV 70 80 90 100 110 120 VQGVNGFEAEFSKSDSSFHLRKASVHWSDSAVYFCAVSAKGTGSKLSFGKGAKLTVSPNI 130 140 150 160 170 180 QNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSA 190 200 210 VAWSNKSDFACANAFNNSIIPEDTFFPSPESS

4. T cell receptor beta T cell receptor beta TRBV13	10 20 30 40 50 60 MGEAAVTQSPRNKVTVTGGNVTLSCRQTNSHNYMYWYRQDTGHGLRLIHYSYGAGNLQIG 70 80 90 100 110 120 DVPDGYKATRTTQEDFFLLLELASPSQTSLYFCASSDAPGQLYFGEGSKLTVLEDLKNVF 130 140 150 160 170 180 PPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQP 190 200 210 220 230 240 ALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWG RAD

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.

Clicking on the clipboard icon will copy the url for the data to your clipboard.

This can then be used to load the structure/data directly from the url into an application like PyMol (for 3D structures) using the load command:

e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif

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]

3TFK assembly 1

Components

MHC Class I alpha chain [cif]

3TFK assembly 1

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

3TFK assembly 1

Peptide only [cif]

3TFK assembly 1

Derived data

Data for this page [json]

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

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.