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4O2E

HLA-B*39:01 binding "SHVAVENAL" at 1.98Å 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', 'E']
2. Class I alpha
HLA-B*39:01
['A', 'D']
3. Peptide
SHVAVENAL
['C', 'F']

Species


Locus / Allele group


Publication

N��-terminal acetylation for T cell recognition: molecular basis of MHC class I-restricted n��-acetylpeptide presentation.

Sun M, Liu J, Qi J, Tefsen B, Shi Y, Yan J, Gao GF
J. Immunol. (2014) 192, 5509-19 [doi:10.4049/jimmunol.1400199]  [pubmed:24829406

As one of the most common posttranslational modifications (PTMs) of eukaryotic proteins, N(α)-terminal acetylation (Nt-acetylation) generates a class of N(α)-acetylpeptides that are known to be presented by MHC class I at the cell surface. Although such PTM plays a pivotal role in adjusting proteolysis, the molecular basis for the presentation and T cell recognition of N(α)-acetylpeptides remains largely unknown. In this study, we determined a high-resolution crystallographic structure of HLA (HLA)-B*3901 complexed with an N(α)-acetylpeptide derived from natural cellular processing, also in comparison with the unmodified-peptide complex. Unlike the α-amino-free P1 residues of unmodified peptide, of which the α-amino group inserts into pocket A of the Ag-binding groove, the N(α)-linked acetyl of the acetylated P1-Ser protrudes out of the groove for T cell recognition. Moreover, the Nt-acetylation not only alters the conformation of the peptide but also switches the residues in the α1-helix of HLA-B*3901, which may impact the T cell engagement. The thermostability measurements of complexes between N(α)-acetylpeptides and a series of MHC class I molecules derived from different species reveal reduced stability. Our findings provide the insight into the mode of N(α)-acetylpeptide-specific presentation by classical MHC class I molecules and shed light on the potential of acetylepitope-based immune intervene and vaccine development.

Structure deposition and release

Deposited: 2013-12-17
Released: 2014-07-23
Revised: 2014-07-23

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: SHVAVENAL

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

TYR59
TYR7
MET5
TYR99
ASN63
TYR159
TRP167
PHE33
ARG62
TYR171
P2 HIS

VAL34
TYR159
CYS67
ASN70
TYR9
GLU45
TYR7
TYR99
SER24
ASN63
ILE66
P3 VAL

TYR99
LEU156
ILE66
TYR159
ARG97
TYR9
P4 ALA

ILE66
P5 VAL

VAL152
GLN155
ASN70
ARG97
LEU156
P6 GLU

THR69
THR73
ASN70
P7 ASN

GLN155
THR73
TRP147
ALA150
SER77
VAL152
P8 ALA

LYS146
TRP147
SER77
ASN80
THR73
GLU76
THR143
P9 LEU

LEU95
TRP147
THR143
SER77
LYS146
PHE116
LEU81
TYR123
ASN80
TYR84

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
ASN63
ILE66
TYR7
B Pocket

SER24
VAL34
GLU45
ASN63
ILE66
CYS67
TYR7
ASN70
TYR9
TYR99
C Pocket

ASN70
THR73
ASP74
TYR9
ARG97
D Pocket

ASN114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

ASN114
TRP147
VAL152
LEU156
ARG97
F Pocket

PHE116
TYR123
THR143
LYS146
TRP147
SER77
ASN80
LEU81
TYR84
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
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-B*39:01
IPD-IMGT/HLA
[ipd-imgt:HLA32458]
        10        20        30        40        50        60
GSHSMRYFYTSVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPREEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DRNTQICKTNTQTDRESLRNLRGYYNQSEAGSHTLQRMYGCDVGPDGRLLRGHNQFAYDG
       130       140       150       160       170       180
KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRTYLEGTCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRW

3. Peptide
SHVAVENAL


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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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]
  1. 4O2E assembly 1  
  2. 4O2E assembly 2  

Components

MHC Class I alpha chain [cif]
  1. 4O2E assembly 1  
  2. 4O2E assembly 2  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 4O2E assembly 1  
  2. 4O2E assembly 2  
Peptide only [cif]
  1. 4O2E assembly 1  
  2. 4O2E assembly 2  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/4o2e

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