CLASS I HISTOCOMPATIBILITY ANTIGEN (HLA-A2.1)/BETA 2-MICROGLOBULIN/PEPTIDE P1049 COMPLEX


Tab-View Sample


MHC-Binding
Epitope  
   
Complex PDB ID 1B0G
Accession Number 3DIEP0578
IEDB ID 2999
Epitope Sequence ALWGFFPVL
Starting Position1
Ending Position9
Epitope Type Linear Epitope

Assay Information  
Assay Antigen Purified MHC - X-ray crystallography Structure (crystal; NMR; etc.)
PDB CategoryHISTOCOMPATIBILITY ANTIGEN
Keyword CLASS I HISTOCOMPATIBILITY ANTIGEN (HLA-A2.1)/BETA 2-MICROGLOBULIN/PEPTIDE P1049 COMPLEX
Antibody Residues Interacting with Antigen Open in new window      Download dimplot pdb file
Antibody Chain 1 PDB Chain A
Antigen PDB ChainC
CommentsThe crystal structure of HLA-A*0201 complexed with the epitope p1049 was determined using the molecular replacement method. The epitope complexed with A2 is recognized by TCR AHIII12.2 from a CD8+ CTL clone derived from a C57BL/6 mouse injected with the human lymphoblastoid cell line JY. There are two molecules in the crystallographic asymmetric unit. PDB chains for each complex are: Complex I : MHC a-chain: A; ß2-m chain: B; epitope chain: C. Complex II : MHC a-chain: d; ß2-m chain: e; epitope chain: F. Epitope main chain density is relatively weak near residue P5. This may indicate some flexibility around the middle of the peptide.

Experimental Details
Method
X-RAY DIFFRACTION
Resolution
2.5
R-Value
0.26
Space Group
P 1
Unit Cell
Length(Å) Angle(°)
a = 50.09 α = 81.98
b = 62.89 β = 76.18
c = 74.68 γ = 77.86



Source Information  
Structure Determination Method X-RAY DIFFRACTION
Host OrganismEscherichia coli
Host Organism StrainBL21 PLYSS
Host Taxonomic ID 562
PlasmidPLM1
  

Ligand non-polymer
 

Sequence


Protein Name
CLASS I HISTOCOMPATIBILITY ANTIGEN (HLA-A2.1)/BETA 2-MICROGLOBULIN/PEPTIDE P1049 COMPLEX
Poly type
polypeptide(L)
Sequence status
Complete

Primary Sequence

Entity ID
1
Chain ID
A,D
Source Method
genetically manipulated
Molecule Name
CLASS I HISTOCOMPATIBILITY ANTIGEN
Sequence Length
275

G S H S M R Y F F T S V S R P G R G E P R F I A V G Y V D D T Q F V R F D S D A A S Q R M E P R A P W I E Q E G P E Y W D G E T R K V K A H S Q T H R V D L G T L R G Y Y N Q S E A G S H T V Q R M Y G C D V G S D W R F L R G Y H Q Y A Y D G K D Y I A L K E D L R S W T A A D M A A Q T T K H K W E A A H V A E Q L R A Y L E G T C V E W L R R Y L E N G K E T L Q R T D A P K T H M T H H A V S D H E A T L R C W A L S F Y P A E I T L T W Q R D G E D Q T Q D T E L V E T R P A G D G T F Q K W A A V V V P S G Q E Q R Y T C H V Q H E G L P K P L T L R W E
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)
Primary Sequence

Entity ID
2
Chain ID
B,E
Source Method
genetically manipulated
Molecule Name
BETA 2-MICROGLOBULIN
Sequence Length
100

M I Q R T P K I Q V Y S R H P A E N G K S N F L N C Y V S G F H P S D I E V D L L K N G E R I E K V E H S D L S F S K D W S F Y L L Y Y T E F T P T E K D E Y A C R V N H V T L S Q P K I V K W D R D M
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)
Primary Sequence

Entity ID
3
Chain ID
C,F
Source Method
genetically manipulated
Molecule Name
PEPTIDE P1049 (ALWGFFPVL)
Sequence Length
9

A L W G F F P V L
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)

X-RAY DIFFRACTION

Crystalization

pH
6.5
pH details
PROTEIN WAS CRYSTALLIZED IN THE HANGING DROP VAPOR DIFFUSION METHOD. THE RESERVOIR SOLUTION CONTAINED 12-16% PEG6000, 6% DIOXANE IN 25MM MES BUFFER, PH6.5. THE HANGING DROP WAS A 1:1 MIXTURE OF THE RESERVOIR SOLUTION AND THE PROTEIN SOLUTION WHICH CONTAINED 10MG/ML PROTEIN IN 25MM MES BUFFER, PH6.5., vapor diffusion - hanging drop


Crystal Data
Unit Cell
Space group
P 1
Length
Angle
°
a  =
50.09
α  =
81.98
b  =
62.89
β  =
76.18
c  =
74.68
γ  =
77.86


Diffraction
Diffraction Detector
Diffraction radiation
Detector
IMAGE PLATE
Monochromator
NI FILTER
Type
RIGAKU RU200
Diffraction Source
Detail
MIRRORS
Source
ROTATING ANODE
Collection date
5/15/1997
Type
RIGAKU RU200


Refinement Data
Reflection Details
Structure Solution Method
MOLECULAR REPLACEMENT
Percent Possible(Observed)
82.6
Resolution(High)
2.5
R-Factor(Observed)
0.26
Cut-off Sigma(F)
0
R-Work
0.255
Number Reflections(Observed)
27079
R-Free
No. of Non-Hydrogen atoms
Used in Refinement
Protein atom
6320
Nucleic acid atom
0
Heterogen Atoms
0
Solvent Atoms
50
Total Atoms
6370


Software and Computing
Computing
Software
Data Reduction (intensity integration)
DENZO
model building
NI FILTER
Data Reduction (data scaling)
SCALEPACK
refinement
REFMAC
Structure Solution
AMORE
Structure Refinement
REFMAC

GO functional annotation for 1b0g

  Cellular component Chain(s)
  0005576  
  extracellular region
B, E 
  0035580  
  specific granule lumen
B, E 
  0005615  
  extracellular space
B, E 
  0009986  
  cell surface
B, E 
  0016020  
  membrane
B, E 
  0005886  
    plasma membrane
B, E 
  0070062  
    extracellular vesicular exosome
B, E 
  0009897  
      external side of plasma membrane
B, E 
  0005794  
        Golgi apparatus
B, E 
  0005829  
        cytosol
B, E 
  0005788  
        endoplasmic reticulum lumen
B, E 
  0042612  
        MHC class I protein complex
B, E 
  0000139  
          Golgi membrane
B, E 
  0031901  
          early endosome membrane
B, E 
  0055038  
            recycling endosome membrane
B, E 
  0031905  
            early endosome lumen
B, E 
  0005925  
            focal adhesion
B, E 
  0030670  
              phagocytic vesicle membrane
B, E 
  0012507  
              ER to Golgi transport vesicle membrane
B, E 
  1904724  
  ?
B, E 
  1990712  
  ?
B, E 
  Biological process Chain(s)
  0002376  
  immune system process
B, E 
  0071281  
  cellular response to iron ion
B, E 
  0071283  
  cellular response to iron(III) ion
B, E 
  1900121  
  negative regulation of receptor binding
B, E 
  1900122  
  positive regulation of receptor binding
B, E 
  0006955  
  immune response
B, E 
  0042493  
    response to drug
B, E 
  0045087  
  innate immune response
B, E 
  0050776  
    regulation of immune response
B, E 
  0002237  
    response to molecule of bacterial origin
B, E 
  0002474  
      antigen processing and presentation of peptide antigen via MHC class I
B, E 
  0044267  
      cellular protein metabolic process
B, E 
  0019885  
        antigen processing and presentation of endogenous peptide antigen via MHC class I
B, E 
  0032092  
        positive regulation of protein binding
B, E 
  0046686  
        response to cadmium ion
B, E 
  0001895  
        retina homeostasis
B, E 
  0050690  
        regulation of defense response to virus by virus
B, E 
  0002479  
          antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
B, E 
  0002480  
          antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
B, E 
  0002481  
          antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent
B, E 
  0045646  
          regulation of erythrocyte differentiation
B, E 
  0048260  
          positive regulation of receptor-mediated endocytosis
B, E 
  0060333  
          interferon-gamma-mediated signaling pathway
B, E 
  0043312  
        neutrophil degranulation
B, E 
  0042026  
          protein refolding
B, E 
  0006826  
            iron ion transport
B, E 
  0010977  
            negative regulation of neuron projection development
B, E 
  0055072  
              iron ion homeostasis
B, E 
  0002726  
              positive regulation of T cell cytokine production
B, E 
  0033077  
              T cell differentiation in thymus
B, E 
  0001916  
              positive regulation of T cell mediated cytotoxicity
B, E 
  0033216  
                ferric iron import
B, E 
  1903991  
  ?
B, E 
  1904434  
  ?
B, E 
  1904437  
  ?
B, E 
  Biochemical function Chain(s)
  0005515  
  protein binding
B, E 
  0001948  
    glycoprotein binding
B, E 
  0042802  
    identical protein binding
B, E 


Literature reference

Title
Structural evidence of T cell xeno-reactivity in the absence of molecular mimicry.
Authors
Journal
Year
Journal Volume
First Page
Last Page
PubMed Abstract
The T cell receptor (TCR); from a xeno-reactive murine cytotoxic T lymphocyte clone AHIII12.2; recognizes murine H-2Db complexed with peptide p1027 (FAPGVFPYM); as well as human HLA-A2.1 complexed with peptide p1049 (ALWGFFPVL). A commonly proposed model (the molecular mimicry model) used to explain TCR cross-reactivity suggests that the molecular surfaces of the recognized complexes are similar in shape; charge; or both; in spite of the primary sequence differences. To examine the mechanism of xeno-reactivity of AHIII12.2; we have determined the crystal structures of A2/p1049 and Db/p1027 to 2.5 A and 2.8 A resolution; respectively. The crystal structures show that the TCR footprint regions of the two class I complexes are significantly different in shape and charge. We propose that rather than simple molecular mimicry; unpredictable arrays of common and differential contacts on the two class I complexes are used for their recognition by the same TCR.
PubMed ID
Search related article in PubMed
Keywords
CLASS I HISTOCOMPATIBILITY ANTIGEN (HLA-A2.1)/BETA 2-MICROGLOBULIN/PEPTIDE P1049 COMPLEX




If you are not able to view this pdf please update your Acrobat reader- click here


Ag-Ab Interaction of the1B0G between chain "C" and chain "A"



Download PDB File Download Ag-Ab Interaction PDB File

Aceess tip: Right-mouse click on Jmol to get access to additional Jmol functionality.

For more information or jmol tutorial please click here

Reference :
Herraez, Angel (2006), "Biomolecules in the Computer: Jmol to the Rescue", Biochemistry and Molecular Biology Education 34 (4): 255-261.



Links to external databases and resources



The IEDB contains data related to antibody and T cell epitopes for humans, non-human primates, rodents, and other animal species. Curation of peptidic epitope data relating to all infectious diseases.
Bcipep is collection of the peptides having the role in Humoral immunity. The peptides in the database has varying measure of immunogenicity.This database can assist in the development of method for predicting B cell epitopes, desigining synthetic vaccines and in disease diagnosis.
A DATABASE OF MHC LIGANDS AND PEPTIDE MOTIFS (Ver. 1.0) SYFPEITHI is a database comprising more than 7000 peptide sequences known to bind class I and class II MHC molecules. The entries are compiled from published reports only.
The HIV databases contain data on HIV genetic sequences, immunological epitopes, drug resistance-associated mutations, and vaccine trials. The website also gives access to a large number of tools that can be used to analyze these data. This project is funded by the Division of AIDS of the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). Click on any of the links below to access a database.
The aim of ABCpred server is to predict B cell epitope(s) in an antigen sequence, using artificial neural network. This is the first server developed based on recurrent neural network (machine based technique) using fixed length patterns.
EPIPREDICT is a new and reliable software to predict HLA-class II restricted T cell epitopes and ligands.
Expasy ProtScale ProtScale [Reference / Documentation] allows you to compute and represent the profile produced by any amino acid scale on a selected protein.
MHCBN is a curated database consisting of detailed information about major histocompatibility complex (MHC) binding, non-binding peptides, and T-cell epitopes. Version 4.0 provides information about peptides interacting with TAP and MHC-linked autoimmune diseases.
AntiJen v2.0 is a database containing quantitative binding data for peptides binding to MHC ligands, TCR-MHC complexes, T cell epitopes, TAP, B cell epitope molecules, and immunological protein-protein interactions. AntiJen includes a peptide library, copy numbers, and diffusion coefficient data. All entries are from published experimentally determined data. The database currently holds over 24,000 entries. No data in AntiJen is from prediction experiments.
HLA Peptide Binding Predictions Function: Rank potential 8-mer, 9-mer, or 10-mer peptides based on a predicted half-time of dissociation to HLA class I molecules. The analysis is based on coefficient tables deduced from the published literature by Dr. Kenneth Parker, Children's Hospital Boston (email: kenneth.parker@childrens.harvard.edu ). Another web site for predicting which peptides bind to MHC molecules is SYFPEITHI, developed by Hans-Georg Rammensee's lab.
AllergenOnline provides access to a peer reviewed allergen list and sequence searchable database intended for identifying proteins that may present a potential risk of allergenic cross-reactivity. This website was designed to help in assessing the safety of proteins that may be introduced into foods through genetic engineering or food processing methods.
The I.U.I.S. Allergen Nomenclature Sub-committee operates under the auspices of the International Union of Immunological Societies (I.U.I.S.) and the World Health Organisation (W.H.O.). The objectives of the I.U.I.S. Allergen Nomenclature Sub-committee are to Maintain a unique and unambiguous nomenclature for allergen molecules and Maintain the ‘official list of allergens’.
Superficial is tool for the identification of potential epitopes or binding sites.
UMAS is a server which provides mirrors of a list of various epitope prediction tools and databases.
MAPPP will predict possible antigenic peptides to be processed and finally presented on cell surfaces. This database aides in the prediction of immunodominant T-cell epitopes and is able to predict the proteasomal cleavage of proteins into smaller fragments, and the binding of peptide sequences to MHC class I molecules.
JenPepM is a database of quantitative binding data for immunological protein-peptide interactions, which allows speedy access to binding data through simple on-line interfaces and effective search mechanisms.
Protall database contains biochemical and clinical information about plant food allergens involved in classical IgE-induced hypersensitivity reactions about 77 allergens from 48 plant species. There are many foods for which a case history of an allergic reaction has been reported for which the allergens responsible have not been described. These are not included in the database.
IMGT®, the international ImMunoGeneTics information system is a high-quality integrated knowledge resource specialized in the immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), immunoglobulin superfamily (IgSF), major histocompatibility complex superfamily (MhcSF) and related proteins of the immune system (RPI) of human and other vertebrate species.