A FUNCTIONAL HOT SPOT FOR ANTIGEN RECOGNITION IN A SUPERAGONIST TCR/MHC COMPLEX


Tab-View Sample


T-Cell Epitope
Epitope  
   
Complex PDB ID 1G6R
Accession Number 3DIEP0296
IEDB ID 58773
Epitope Sequence SIYRYYGL
Starting Position1
Ending Position8
Epitope Type Linear Epitope

Assay Information  
Assay Antigen SIYRYYGL
PDB CategoryIMMUNE SYSTEM
Keyword T CELL ANTIGEN RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; SUPERAGONIST; IMMUNE SYSTEM
Antibody Residues Interacting with Antigen Open in new window      Download dimplot pdb file
Antibody Chain 1 PDB Chain A
Antigen PDB ChainP
CommentsThe crystal structure of the ternary complex of the 2C TCR with the epitope bound to H-2Kb was determined. There are two independent complexes in the crystallographic asymmetric unit. PDB chains for each complex are: Complex I : MHC chain: H; MHC ?2-microglobulin chain: L; epitope chain: P; TCR ?-chain: A; MHC ?-chain: B. Complex II : MHC chain: I; MHC ?2-microglobulin chain: M; epitope chain: Q; TCR ?-chain: C; MHC ?-chain: D. In one of the complexes the electron density is highly disordered for the TCR.

Experimental Details
Method
X-RAY DIFFRACTION
Resolution
2.8
R-Value
Space Group
P 21 21 2
Unit Cell
Length(Å) Angle(°)
a = 297.71 α = 90
b = 94.57 β = 90
c = 84.89 γ = 90


Source Information  
Structure Determination Method X-RAY DIFFRACTION
Host OrganismDrosophila melanogaster
Host Taxonomic ID 7227

Ligand L-peptide linking
 

Sequence


Protein Name
A FUNCTIONAL HOT SPOT FOR ANTIGEN RECOGNITION IN A SUPERAGONIST TCR/MHC COMPLEX
Poly type
polypeptide(L)
Sequence status
Complete

Primary Sequence

Entity ID
1
Chain ID
A,C
Source Method
genetically manipulated
Molecule Name
ALPHA T CELL RECEPTOR
Fragment Name
EXTRACELLULAR DOMAIN
Sequence Length
202

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

Entity ID
2
Chain ID
B,D
Source Method
genetically manipulated
Molecule Name
BETA T CELL RECEPTOR
Fragment Name
EXTRACELLULAR DOMAIN
Sequence Length
237

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

Entity ID
3
Chain ID
H,I
Source Method
genetically manipulated
Molecule Name
MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I MOLECULE
Fragment Name
EXTRACELLULAR DOMAIN
Sequence Length
274

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

Entity ID
4
Chain ID
L,M
Source Method
genetically manipulated
Molecule Name
BETA-2 MICROGLOBULIN
Fragment Name
NON-COVALENTLY ASSOCIATED WITH ENTITY 3
Sequence Length
99

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

Entity ID
5
Chain ID
P
Source Method
Synthetic
Molecule Name
SIYR PEPTIDE
Sequence Length
8

S I Y R Y Y G L
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)

X-RAY DIFFRACTION

Crystalization

pH
7.2
pH details
0.2 M Tris/acetate, 10% PEG 6000, pH 7.2, VAPOR DIFFUSION, temperature 22K
temparature
22
temparature Detail


Crystal Data
Unit Cell
Space group
P 21 21 2
Length
Angle
°
a  =
297.71
α  =
90
b  =
94.57
β  =
90
c  =
84.89
γ  =
90


Diffraction
Diffraction Detector
Diffraction radiation
Detector
IMAGE PLATE
Monochromator
Type
SSRL BEAMLINE BL9-1
Diffraction Source
Detail
Source
SYNCHROTRON
Collection date
Type
SSRL BEAMLINE BL9-1


Refinement Data
Reflection Details
Structure Solution Method
MOLECULAR REPLACEMENT
Percent Possible(Observed)
Resolution(High)
2.8
R-Factor(Observed)
Cut-off Sigma(F)
0
R-Work
0.2976
Number Reflections(Observed)
R-Free
No. of Non-Hydrogen atoms
Used in Refinement
Protein atom
13100
Nucleic acid atom
0
Heterogen Atoms
0
Solvent Atoms
0
Total Atoms
13100


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

GO functional annotation for 1g6r



Literature reference

Title
A functional hot spot for antigen recognition in a superagonist TCR/MHC complex.
Authors
Journal
Year
Journal Volume
First Page
Last Page
PubMed Abstract
A longstanding question in T cell receptor signaling is how structurally similar ligands; with similar affinities; can have substantially different biological activity. The crystal structure of the 2C TCR complex of H-2Kb with superagonist peptide SIYR at 2.8 A elucidates a structural basis for TCR discrimination of altered peptide ligands. The difference in antigen potency is modulated by two cavities in the TCR combining site; formed mainly by CDRs 3alpha; 3beta; and 1beta; that complement centrally located peptide residues. This functional hot spot allows the TCR to finely discriminate amongst energetically similar interactions within different ligands for those in which the peptide appropriately stabilizes the TCR/pMHC complex and provides a new structural perspective for understanding differential signaling resulting from T cell cross-reactivity.
PubMed ID
Search related article in PubMed
Keywords
T CELL ANTIGEN RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; SUPERAGONIST; IMMUNE SYSTEM




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Ag-Ab Interaction of the1G6R between chain "P" and chain "A"



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Epitope found in chain   :P                                                                                           
Epitope Sequence:-SIYRYYGL
Epitope Position found in PDB File   :   1-8  (Highlighted in white spacefill model)
S I Y R Y Y G L

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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.
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.