3TJH

Truncated H2-Ld presenting "SPLDSLWWI" to Alpha/Beta T cell receptor at 2.12Å 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
SPLDSLWWI

['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: 2011-08-24

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: SPLDSLWWI

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

MET5

ARG62

TYR99

TYR159

TYR59

TYR7

ILE63

TRP167

P2 PRO

TYR99

TYR159

TYR7

ILE63

VAL66

TYR45

P3 LEU

TYR155

ARG97

VAL66

GLN70

GLU9

GLU114

TYR99

TYR156

TYR159

P4 ASP

TYR156

TYR155

GLN65

ARG97

VAL66

GLN70

P5 SER

GLU114

TYR156

GLN70

GLU9

TYR155

TRP73

ARG97

P6 LEU

TRP73

TYR156

TYR155

P7 TRP

TRP147

GLY151

TRP73

ALA150

ALA152

TYR156

TYR155

P8 TRP

VAL76

LYS146

THR143

ASN77

TRP147

TRP73

P9 ILE

LEU81

TYR123

LEU95

TRP73

LYS146

THR143

ASN77

ILE124

THR80

TRP147

TYR84

PHE116

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	SPLDSLWWI

3. T cell receptor alpha T cell receptor alpha TRAV9	10 20 30 40 50 60 ADPGYLLEAQSVTQPDARVTVSEGASLQLRCKYSYSATPYLFWYVQYPRQGLQMLLKYYS 70 80 90 100 110 120 GDPVVQGVNGFEAEFSKSDSSFHLRKASVHWSDSAVYFCAVSAKGTGSKLSFGKGAKLTV 130 140 150 160 170 180 SPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFK 190 200 210 220 SNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSSRGGLEVLFQ

4. T cell receptor beta T cell receptor beta TRBV13	10 20 30 40 50 60 ADPEAAVTQSPRNKVTVTGGNVTLSCRQTNSHNYMYWYRQDTGHGLRLIHYSYGAGNLQI 70 80 90 100 110 120 GDVPDGYKATRTTQEDFFLLLELASPSQTSLYFCASSDAPGQLYFGEGSKLTVLEDLKNV 130 140 150 160 170 180 FPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQ 190 200 210 220 230 240 PALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAW 250 GRADSRGGLEVLFQ

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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Complete structures

Aligned structures [cif]

3TJH assembly 1

Components

MHC Class I alpha chain [cif]

3TJH assembly 1

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

3TJH assembly 1

Peptide only [cif]

3TJH assembly 1

Derived data

Data for this page [json]

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

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.