8D5N

H2-Ld binding "HPGSVNEFDFGCGGSG" at 1.80Å 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

['F', 'H']

2. Class I alpha
H2-Ld

['C', 'A']

3. Peptide
HPGSVNEFDFGCGGSG

['E', 'B']

Species

Mus musculus (Mouse)

Locus / Allele group

H2-L / H2-Ld

Publication

Peptide Centric Vβ Specific Germline Contacts Shape a Specialist T Cell Response.

Wang Y, Tsitsiklis A, Devoe S, Gao W, Chu HH, Zhang Y, Li W, Wong WK, Deane CM, Neau D, Slansky JE, Thomas PG, Robey EA, Dai S

Front Immunol (2022) 13, 847092 [doi:10.3389/fimmu.2022.847092] [pubmed:35967379]

Certain CD8 T cell responses are particularly effective at controlling infection, as exemplified by elite control of HIV in individuals harboring HLA-B57. To understand the structural features that contribute to CD8 T cell elite control, we focused on a strongly protective CD8 T cell response directed against a parasite-derived peptide (HF10) presented by an atypical MHC-I molecule, H-2Ld. This response exhibits a focused TCR repertoire dominated by Vβ2, and a representative TCR (TG6) in complex with Ld-HF10 reveals an unusual structure in which both MHC and TCR contribute extensively to peptide specificity, along with a parallel footprint of TCR on its pMHC ligand. The parallel footprint is a common feature of Vβ2-containing TCRs and correlates with an unusual Vα-Vβ interface, CDR loop conformations, and Vβ2-specific germline contacts with peptides. Vβ2 and Ld may represent "specialist" components for antigen recognition that allows for particularly strong and focused T cell responses.

Structure deposition and release

Deposited: 2022-06-05

Released: 2022-09-14

Revised: 2022-09-14

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Hexadecamer (16 amino acids)

Sequence: HPGSVNEFDFGCGGSG

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 HIS

TYR159

ARG62

TYR7

TRP167

MET5

PHE33

TYR59

ILE63

TYR171

GLU163

ILE66

P10 PHE

THR80

ILE124

TRP73

LYS146

THR143

PHE116

LEU81

TRP147

ILE142

ASN77

TYR123

LEU95

P11 GLY

ILE142

ASN77

CYS84

THR80

LYS146

THR143

P12 CYS

LEU81

ILE142

ALA139

THR80

CYS84

TYR123

THR143

P13 GLY

LYS146

ILE142

CYS84

P14 GLY

ILE142

LYS146

P2 PRO

GLU163

ILE66

TYR159

TYR7

TYR45

GLU9

ILE63

TYR99

P3 GLY

GLN70

TYR99

ILE66

TYR159

TRP97

GLU9

P4 SER

ILE66

GLN70

TRP97

P5 VAL

ILE66

GLY69

GLN65

TRP73

GLN70

P6 ASN

PHE74

TRP73

TRP97

TYR156

PHE116

GLN70

P7 GLU

TYR155

P8 PHE

TYR155

TRP147

TRP73

GLY151

ASN77

ALA150

ALA152

P9 ASP

ASN77

VAL76

TRP73

THR143

TRP147

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

GLU163

TRP167

TYR171

MET5

TYR59

ILE63

ILE66

TYR7

B Pocket

SER24

VAL34

TYR45

ILE63

ILE66

ALA67

TYR7

GLN70

GLU9

TYR99

C Pocket

GLN70

TRP73

PHE74

GLU9

TRP97

D Pocket

GLU114

TYR155

TYR156

TYR159

LEU160

TYR99

E Pocket

GLU114

TRP147

ALA152

TYR156

TRP97

F Pocket

PHE116

TYR123

THR143

LYS146

TRP147

ASN77

THR80

LEU81

CYS84

LEU95

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 GGSGGIQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMS 70 80 90 100 FSKDWSFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDM

2. Class I alpha H2-Ld	10 20 30 40 50 60 GPHSMRYFETAVSRPGLGEPRYISVGYVDNKEFVRFDSDAENPRYEPQAPWMEQEGPEYW 70 80 90 100 110 120 ERITQIAKGQEQWFRVNLRTLLGCYNQSAGGTHTLQWMYGCDVGSDGRLLRGYEQFAYDG 130 140 150 160 170 180 SDYIALNEDLKTWTAADMAAQITRRKWEQAGAAEYYRAYLEGECVEWLHRYLKNGNATLL 190 200 210 220 230 240 RTDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGT 250 260 270 280 FQKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWQSTRGGAS

3. Peptide	HPGSVNEFDFGCGGSG

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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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/8d5n

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.