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1W72

HLA-A*01:01 binding "EADPTGHSY" with antibody at 2.15Å 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 antibody

1. ab_heavy
['I']
2. ab_light
['M']
3. Beta 2 microglobulin
['B', 'E']
4. Class I alpha
HLA-A*01:01
['A', 'D']
5. Peptide
EADPTGHSY
['C', 'F']

Species


Locus / Allele group


Publication

A major histocompatibility complex-peptide-restricted antibody and t cell receptor molecules recognize their target by distinct binding modes: crystal structure of human leukocyte antigen (HLA)-A1-MAGE-A1 in complex with FAB-HYB3.

H��lsmeyer M, Chames P, Hillig RC, Stanfield RL, Held G, Coulie PG, Alings C, Wille G, Saenger W, Uchanska-Ziegler B, Hoogenboom HR, Ziegler A
J. Biol. Chem. (2005) 280, 2972-80 [doi:10.1074/jbc.m411323200]  [pubmed:15537658

Antibodies with T cell receptor-like specificity possess a considerable diagnostic and therapeutic potential, but the structural basis of the interaction between an antibody and an histocompatibility antigen has so far not been determined. We present here the crystal structure (at 2.15 A resolution) of the recombinant, affinity-matured human antibody fragment Fab-Hyb3 bound to the tumor-associated human leukocyte antigen (HLA)/peptide complex HLA-A1.MAGE-A1. Fab-Hyb3 employs a diagonal docking mode resembling that of T cell receptors. However, other than these natural ligands, the antibody uses only four of its six complementarity-determining regions for direct interactions with the target. It recognizes the C-terminal half of the MAGE-A1 peptide, the HLA-A1 alpha1-helix, and N-terminal residues of the alpha2-helix, accompanied by a large tilting angle between the two types of molecules within the complex. Interestingly, only a single hydrogen bond between a peptide side chain and Fab-Hyb3 contributes to the interaction, but large buried surface areas with pronounced shape complementarity assure high affinity and specificity for MAGE-A1. The HLA-A1.MAGE-A1.antibody structure is discussed in comparison with those of natural ligands recognizing HLA.peptide complexes.

Structure deposition and release

Deposited: 2004-08-27
Released: 2004-11-09
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: EADPTGHSY

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 GLU

PHE33
GLN62
GLY167
TYR171
TYR7
GLU63
TYR159
TYR59
ARG163
ARG170
CYS164
MET5
P2 ALA

ASN66
MET67
TYR159
TYR99
TYR7
GLU63
P3 ASP

ASN66
ARG114
ARG156
TYR159
TYR99
P4 PRO

TYR159
ASN66
P5 THR

ARG156
GLN155
P6 GLY

ARG156
THR73
P7 HIS

VAL150
TRP147
ALA152
ARG156
GLN155
THR73
ASN77
P8 SER

THR143
LYS146
THR73
THR80
ASN77
TRP147
P9 TYR

ILE95
ILE142
ASN77
TRP147
TYR84
THR143
TYR123
LYS146
ASP116
ILE124
ILE97
THR80
LEU81

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
ARG163
GLY167
TYR171
MET5
TYR59
GLU63
ASN66
TYR7
B Pocket

ALA24
VAL34
MET45
GLU63
ASN66
MET67
TYR7
HIS70
PHE9
TYR99
C Pocket

HIS70
THR73
ASP74
PHE9
ILE97
D Pocket

ARG114
GLN155
ARG156
TYR159
LEU160
TYR99
E Pocket

ARG114
TRP147
ALA152
ARG156
ILE97
F Pocket

ASP116
TYR123
THR143
LYS146
TRP147
ASN77
THR80
LEU81
TYR84
ILE95

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. ab_heavy
ab_heavy
        10        20        30        40        50        60
EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGY
        70        80        90       100       110       120
ADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGRGFHYYYYGMDIWGQGTTVTV
       130       140       150       160       170       180
SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
       190       200       210       220
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPK

2. ab_light
ab_light
        10        20        30        40        50        60
SYVLTQPPSVSVAPGQTARITCGGNNIGSRSVHWYQQKPGQAPVLVVYDDSDRPSGIPER
        70        80        90       100       110       120
FSGSNSGNMATLTISRVEAGDEADYYCQVWDSRTDHWVFGGGTDLTVLGQPKAAPSVTLF
       130       140       150       160       170       180
PPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYL
       190       200
SLTPEQWKSHRSYSCQVTHEGSTVEKTVAP

3. Beta 2 microglobulin
Beta 2 microglobulin
        10        20        30        40        50        60
MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD
        70        80        90
WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

4. Class I alpha
HLA-A*01:01
IPD-IMGT/HLA
[ipd-imgt:HLA34767]
        10        20        30        40        50        60
GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQKMEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DQETRNMKAHSQTDRANLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYDG
       130       140       150       160       170       180
KDYIALNEDLRSWTAADMAAQITKRKWEAVHAAEQRRVYLEGRCVDGLRRYLENGKETLQ
       190       200       210       220       230       240
RTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT
       250       260       270
FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRW

5. Peptide
EADPTGHSY


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. 1W72 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 1W72 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 1W72 assembly 1  
Peptide only [cif]
  1. 1W72 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/1w72

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