CRYSTAL STRUCTURE OF HLA-A*0201 COMPLEXED WITH A PEPTIDE WITH THE CARBOXYL-TERMINAL GROUP SUBSTITUTED BY A METHYL GROUP


Tab-View Sample


MHC-Binding
Epitope  
   
Complex PDB ID 1B0R
Accession Number 3DIEP0337
IEDB ID 20351
Epitope Sequence GILGFVFTL
Starting Position701
Ending Position706
Epitope Type Linear Epitope

Assay Information  
Assay Antigen Purified MHC - X-ray crystallography Structure (crystal; NMR; etc.)
PDB CategorySIGNALING PROTEIN
Keyword HLA-A2; ANTIGENIC PEPTIDES; CLASS I MHC MOLECULES; HLA-A2 COMPLEXES; HYDROGEN BONDS; PROTEIN STRUCTURE; SIGNALING PROTEIN
Antibody Residues Interacting with Antigen Open in new window      Download dimplot pdb file
Antibody Chain 1 PDB Chain A
Antigen PDB ChainC
CommentsNo interpretable electron density was observed at the P4-Gly and P5-Phe positions of the peptide.

Experimental Details
Method
X-RAY DIFFRACTION
Resolution
2.9
R-Value
0.253
Space Group
P 21 21 21
Unit Cell
Length(Å) Angle(°)
a = 49.6 α = 90
b = 74.4 β = 90
c = 121.4 γ = 90



Source Information  
Structure Determination Method X-RAY DIFFRACTION
Host OrganismEscherichia coli
Host Organism StrainXA90
Host Taxonomic ID 562
PlasmidPHN1
  

Ligand L-peptide linking
 

Sequence


Protein Name
CRYSTAL STRUCTURE OF HLA-A*0201 COMPLEXED WITH A PEPTIDE WITH THE CARBOXYL-TERMINAL GROUP SUBSTITUTED BY A METHYL GROUP
Poly type
polypeptide(L)
Sequence status
Complete

Primary Sequence

Entity ID
1
Chain ID
A
Source Method
genetically manipulated
Molecule Name
PROTEIN (HLA-A*0201)
Fragment Name
EXTRACELLULAR DOMAINS ALPHA 1,ALPHA 2 AND ALPHA 3
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
Source Method
genetically manipulated
Molecule Name
PROTEIN (HLA-A*0201)
Fragment 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
Source Method
Synthetic
Molecule Name
PROTEIN (INFLUENZA MATRIX PEPTIDE)
Sequence Length
9

G I L G F V F T C D E
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)

X-RAY DIFFRACTION

Crystalization

pH
6.5
pH details
pH 6.50


Crystal Data
Unit Cell
Space group
P 21 21 21
Length
Angle
°
a  =
49.6
α  =
90
b  =
74.4
β  =
90
c  =
121.4
γ  =
90


Diffraction
Diffraction Detector
Diffraction radiation
Detector
IMAGE PLATE
Monochromator
Type
Diffraction Source
Detail
Source
Collection date
Type


Refinement Data
Reflection Details
Structure Solution Method
MOLECULAR REPLACEMENT
Percent Possible(Observed)
90.5
Resolution(High)
2.9
R-Factor(Observed)
0.253
Cut-off Sigma(F)
2
R-Work
0.253
Number Reflections(Observed)
8304
R-Free
No. of Non-Hydrogen atoms
Used in Refinement
Protein atom
3092
Nucleic acid atom
0
Heterogen Atoms
0
Solvent Atoms
0
Total Atoms
3092


Software and Computing
Computing
Software
Data Reduction (intensity integration)
DENZO
model building
Data Reduction (data scaling)
SCALEPACK
refinement
X-PLOR 3.1
Structure Solution
X-PLOR
Structure Refinement
X-PLOR 3.1

GO functional annotation for 1b0r

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


Literature reference

Title
Crystal structures of HLA-A*0201 complexed with antigenic peptides with either the amino- or carboxyl-terminal group substituted by a methyl group.
Authors
Journal
Year
Journal Volume
First Page
Last Page
PubMed Abstract
The crystal structures of class I major histocompatibility complex (MHC) molecules complexed with antigenic peptides revealed a network of hydrogen bonds between the charged amino- and carboxyl-termini of the peptides and conserved MHC residues at both ends of the peptide binding site. These interactions were shown to contribute substantially to the stability of class I MHC/peptide complexes by thermal denaturation studies using synthetic peptides in which either the amino- or carboxyl-terminal group is substituted by a methyl group. Here we report crystal structures of HLA-A*0201 complexed with these terminally modified synthetic peptides showing that they adopt the same bound conformation as antigenic peptides. A number of variations in peptide conformation were observed for the terminally modified peptides; including in one case; a large conformational difference in four central peptide residues that is apparently caused by the lattice contact. This is reminiscent of the way binding a T-cell receptor changed the conformation of central residues of an MHC-bound peptide. The structures determined identify which conserved hydrogen bonds are eliminated in terminally substituted peptides and suggest an increased energetic importance of the interactions at the peptide termini for MHC-peptide stability.
PubMed ID
Search related article in PubMed
Keywords
HLA-A2; ANTIGENIC PEPTIDES; CLASS I MHC MOLECULES; HLA-A2 COMPLEXES; HYDROGEN BONDS; PROTEIN STRUCTURE; SIGNALING PROTEIN




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Ag-Ab Interaction of the1B0R between chain "C" and chain "A"



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Epitope found in chain   :C                                                                                           
Epitope Sequence:-GILGFVFTL
Epitope Position found in PDB File   :   701-706  (Highlighted in white spacefill model)
G I L G F V F T C D E

Download PDB File Download Ag-Ab Interaction PDB File

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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.