X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB


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MHC-Binding
Epitope  
   
Complex PDB ID 1D5M
Accession Number 3DIEP0458
IEDB ID 94970
Epitope Sequence XRAMXSX
Starting Position803
Ending Position810
Epitope Type Linear Epitope

Assay Information  
Assay Antigen "Purified MHC - X-ray crystallography Structure (crystal; NMR; etc.)"
PDB CategoryIMMUNE SYSTEM
Keyword COMPLEX (MHC CLASS II/SUPERANTIGEN); IMMUNE SYSTEM
Antibody Residues Interacting with Antigen Open in new window      Download dimplot pdb file
Antibody Chain 1 PDB Chain A
Antigen PDB ChainD
CommentsThe crystal structure contains the MHC/epitope complex bound to the superantigen (SAG) staphylococcal enterotoxin B (SEB). SAG PDB chain is D. The SAG was included in the complex as a vehicle to form crystals of MHC with novel compounds that diffract well. Clear electron density is observed for the MHC residues except for a loop consisting of residues B:105-112 and for the SAG molecule for a loop consisting of residues 99-108.

Experimental Details
Method
X-RAY DIFFRACTION
Resolution
2
R-Value
0.236
Space Group
P 21 21 21
Unit Cell
Length(Å) Angle(°)
a = 82.38 α = 90
b = 93.34 β = 90
c = 99.68 γ = 90


Source Information  
Structure Determination Method X-RAY DIFFRACTION
Source Organism Staphylococcus aureus
Taxonomic ID1280
Entity ID3
Host OrganismDrosophila melanogaster
Host Taxonomic ID 7227

Ligand non-polymer
 
Ligand NameACETYL GROUP
Chem Name ACE
Ligand NameN-ACETYL-D-GLUCOSAMINE
Chem Name NAG

Sequence


Protein Name
N-ACETYL-D-GLUCOSAMINE
Poly type
polypeptide(L)
Sequence status
Complete

Primary Sequence

Entity ID
1
Chain ID
A
Source Method
genetically manipulated
Molecule Name
HLA CLASS II HISTOCOMPATIBILITY ANTIGEN
Fragment Name
DR ALPHA CHAIN, EXTRACELLULAR DOMAIN
Sequence Length
181

I K E E H V I I Q A E F Y L N P D Q S G E F M F D F D G D E I F H V D M A K K E T V W R L E E F G R F A S F E A Q G A L A N I A V D K A N L E I M T K R S N Y T P I T N V P P E V T V L T N S P V E L R E P N V L I C F I D K F T P P V V N V T W L R N G K P V T T G V S E T V F L P R E D H L F R K F H Y L P F L P S T E D V Y D C R V E H W G L D E P L L K H W E F D
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
HLA CLASS II HISTOCOMPATIBILITY ANTIGEN
Fragment Name
DR-4 BETA CHAIN, EXTRACELLULAR DOMAIN
Sequence Length
192

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

Entity ID
3
Chain ID
C
Source Method
Natural
Molecule Name
ENTEROTOXIN TYPE B
Sequence Length
239

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

Entity ID
4
Chain ID
D
Source Method
Synthetic
Molecule Name
PEPTIDE INHIBITOR
Sequence Length
8

A C E A L C R A M C Y S C L E
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)

X-RAY DIFFRACTION

Crystalization

pH
7.4
pH details
5% PEG 4000, 0.01 M NA ACETATE, PH 5, 2.4% ETHYLENE GLYCOL, pH 7.4


Crystal Data
Unit Cell
Space group
P 21 21 21
Length
Angle
°
a  =
82.38
α  =
90
b  =
93.34
β  =
90
c  =
99.68
γ  =
90


Diffraction
Diffraction Detector
Diffraction radiation
Detector
IMAGE PLATE
Monochromator
Type
NSLS BEAMLINE X4A
Diffraction Source
Detail
Source
SYNCHROTRON
Collection date
1/1/1994
Type
NSLS BEAMLINE X4A


Refinement Data
Reflection Details
Structure Solution Method
MOLECULAR REPLACEMENT
Percent Possible(Observed)
92.9
Resolution(High)
2
R-Factor(Observed)
0.236
Cut-off Sigma(F)
0
R-Work
0.236
Number Reflections(Observed)
48815
R-Free
No. of Non-Hydrogen atoms
Used in Refinement
Protein atom
4917
Nucleic acid atom
0
Heterogen Atoms
14
Solvent Atoms
145
Total Atoms
5076


Software and Computing
Computing
Software
Data Reduction (intensity integration)
DENZO
model building
Data Reduction (data scaling)
SCALEPACK
refinement
CNS 0.9
Structure Solution
AMORE
Structure Refinement
CNS 0.9

GO functional annotation for 1d5m

  Cellular component Chain(s)
  0005576  
  extracellular region
  0016020  
  membrane
A, B 
  0042613  
    MHC class II protein complex
A, B 
  Biological process Chain(s)
  0006955  
  immune response
A, B 
  0019882  
  antigen processing and presentation
A, B 
  0009405  
    pathogenesis


Literature reference

Title
Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures.
Authors
Journal
Year
Journal Volume
First Page
Last Page
PubMed Abstract
Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design; resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays; resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods; peptide analogue SAR; peptide mimetics substitutions; and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.
PubMed ID
Search related article in PubMed
Keywords
COMPLEX (MHC CLASS II/SUPERANTIGEN); IMMUNE SYSTEM




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Ag-Ab Interaction of the1D5M between chain "D" and chain "A"



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Epitope found in chain   :D                                                                                           
Epitope Sequence:-XRAMXSX
Epitope Position found in PDB File   :   803-810  (Highlighted in white spacefill model)
A C E A L C R A M C Y S C L 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.