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5IRO

HLA-A*02:01 binding "LLFGYPVYV" with Human adenovirus type 4 E3-19K at 2.64Å 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 and e319k

1. Beta 2 microglobulin
['C', 'G', 'K', 'O', 'S', 'W']
2. Class I alpha
HLA-A*02:01
['A', 'E', 'I', 'M', 'Q', 'U']
3. e319k
['D', 'H', 'L', 'P', 'T', 'X']
5. Peptide
LLFGYPVYV
['B', 'F', 'J', 'N', 'R', 'V']

Species

Locus / Allele group

HLA-A / HLA-A*02

Publication

Structure of the Adenovirus Type 4 (Species E) E3-19K/HLA-A2 Complex Reveals Species-Specific Features in MHC Class I Recognition.

Li L, Santarsiero BD, Bouvier M
J. Immunol. (2016) 197, 1399-407 [doi:10.4049/jimmunol.1600541]  [pubmed:27385781] 

Adenoviruses (Ads) subvert MHC class I Ag presentation and impair host anti-Ad cellular activities. Specifically, the Ad-encoded E3-19K immunomodulatory protein targets MHC class I molecules for retention within the endoplasmic reticulum of infected cells. We report the x-ray crystal structure of the Ad type 4 (Ad4) E3-19K of species E bound to HLA-A2 at 2.64-Å resolution. Structural analysis shows that Ad4 E3-19K adopts a tertiary fold that is shared only with Ad2 E3-19K of species C. A comparative analysis of the Ad4 E3-19K/HLA-A2 structure with our x-ray structure of Ad2 E3-19K/HLA-A2 identifies species-specific features in HLA-A2 recognition. Our analysis also reveals common binding characteristics that explain the promiscuous, and yet high-affinity, association of E3-19K proteins with HLA-A and HLA-B molecules. We also provide structural insights into why E3-19K proteins do not associate with HLA-C molecules. Overall, our study provides new information about how E3-19K proteins selectively engage with MHC class I to abrogate Ag presentation and counteract activation of CD8(+) T cells. The significance of MHC class I Ag presentation for controlling viral infections, as well as the threats of viral infections in immunocompromised patients, underline our efforts to characterize viral immunoevasins, such as E3-19K.

Structure deposition and release

Deposited: 2016-03-14
Released: 2016-08-24
Revised: 2019-12-11

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: LLFGYPVYV

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 LEU

CYS164
TYR7
TYR171
TYR159
THR163
TYR59
GLU63
TRP167
PHE33
 P2 LEU

VAL67
PHE9
TYR7
TYR99
TYR159
GLU63
LYS66
HIS70
 P3 PHE

TYR159
LYS66
GLN155
LEU156
HIS70
TYR99
 P4 GLY

LYS66
 P5 TYR

GLN155
LEU156
VAL152
 P6 PRO

THR73
 P7 VAL

THR73
TRP147
ASP77
TYR116
ARG97
 P8 TYR

THR73
TRP147
ASP77
TYR116
THR143
LYS146
 P9 VAL

LEU81
TRP147
ASP77
TYR116
THR80
THR143
LYS146

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
MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD
        70        80        90
WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM
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. e319k
e319k
        10        20        30        40        50        60
AVVTEKADPCLTFNPDKCQLSFQPDGNRCAVLIKCGWECQSVAIQYKNKTRNNTLASTWQ
        70        80        90       100
PGDPEWYTVSVPGADGFLRTVNNTFIFEHMCNTAMFMSRQYHMWPPRK
5. Peptide
LLFGYPVYV

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. 5IRO assembly 1  
  2. 5IRO assembly 2  
  3. 5IRO assembly 3  
  4. 5IRO assembly 4  
  5. 5IRO assembly 5  
  6. 5IRO assembly 6  

Components

MHC Class I alpha chain [cif]
  1. 5IRO assembly 1  
  2. 5IRO assembly 2  
  3. 5IRO assembly 3  
  4. 5IRO assembly 4  
  5. 5IRO assembly 5  
  6. 5IRO assembly 6  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 5IRO assembly 1  
  2. 5IRO assembly 2  
  3. 5IRO assembly 3  
  4. 5IRO assembly 4  
  5. 5IRO assembly 5  
  6. 5IRO assembly 6  
Peptide only [cif]
  1. 5IRO assembly 1  
  2. 5IRO assembly 2  
  3. 5IRO assembly 3  
  4. 5IRO assembly 4  
  5. 5IRO assembly 5  
  6. 5IRO assembly 6  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/5iro

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


Creative Commons Licence
This work is licensed under a Creative Commons Attribution 4.0 International License.