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1T22

HLA-A*02:01 binding "SLYNTVATL" at 2.20Å 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.

Information sections


Complex type

Class i with peptide

1. Beta 2 microglobulin
['B']
2. Class I alpha
HLA-A*02:01
['A']
3. Peptide
SLYNTVATL
['C']

Species


Locus / Allele group


Publication

Structural basis for degenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes.

Martinez-Hackert E, Anikeeva N, Kalams SA, Walker BD, Hendrickson WA, Sykulev Y
J. Biol. Chem. (2006) 281, 20205-12 [doi:10.1074/jbc.M601934200]  [pubmed:16702212

It is well established that even small changes in amino acid side chains of antigenic peptide bound to major histocompatibility complex (MHC) protein may completely abrogate recognition of the peptide-MHC (pMHC) complex by the T cell receptor (TCR). Often, however, several nonconservative substitutions in the peptide antigen are accommodated and do not impair its recognition by TCR. For example, a preponderance of natural sequence variants of the human immunodeficiency virus p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes, which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR. Here we study the molecular basis for this degenerate recognition of SL9 variants. We show that several SL9 variants bind comparably well to soluble HLA-A2 and to a particular soluble TCR and that these variants are active in the cognate cytotoxicity assay. Natural SL9 variation is restricted by its context in the HIV p17 matrix protein. High resolution crystal structures of seven selected SL9 variants bound to HLA-A2 all have remarkably similar peptide conformations and side-chain dispositions outside sites of substitution. This preservation of the peptide conformation despite epitope variations suggests a mechanism for the observed degeneracy in pMHC recognition by TCR and may contribute to the persistence of SL9-mediated immune responses in chronically infected individuals.

Structure deposition and release

Deposited: 2004-04-19
Released: 2005-09-06
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: Nonamer (9 amino acids)

Sequence: SLYNTVATL

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

GLU63
LYS66
PHE33
MET5
TYR171
TYR159
TYR59
TYR7
THR163
TRP167
P2 LEU

PHE9
TYR7
HIS70
LYS66
MET45
TYR99
GLU63
TYR159
VAL67
P3 TYR

TYR159
TYR99
VAL152
LEU156
HIS70
LYS66
GLN155
P4 ASN

TYR159
ARG65
LYS66
P5 THR

HIS70
P6 VAL

ALA69
ARG97
THR73
HIS70
P7 ALA

THR73
ASP77
VAL152
ARG97
TRP147
P8 THR

ASP77
LYS146
VAL76
TRP147
THR73
P9 LEU

ASP77
THR80
LEU81
TRP147
TYR84
ILE124
THR143
LYS146
TYR116
TYR123

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
GLU63
LYS66
TYR7
B Pocket

ALA24
VAL34
MET45
GLU63
LYS66
VAL67
TYR7
HIS70
PHE9
TYR99
C Pocket

HIS70
THR73
HIS74
PHE9
ARG97
D Pocket

HIS114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

HIS114
TRP147
VAL152
LEU156
ARG97
F Pocket

TYR116
TYR123
THR143
LYS146
TRP147
ASP77
THR80
LEU81
TYR84
VAL95

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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-A*02:01
IPD-IMGT/HLA
[ipd-imgt:HLA35266]
        10        20        30        40        50        60
GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG
       130       140       150       160       170       180
KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT
       250       260       270
FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWE

3. Peptide
SLYNTVATL


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]
  1. 1T22 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 1T22 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 1T22 assembly 1  
Peptide only [cif]
  1. 1T22 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/1t22

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