CRYSTAL STRUCTURE OF HLA-DR2 (DRA*0101;DRB1*1501) COMPLEXED WITH A PEPTIDE FROM HUMAN MYELIN BASIC PROTEIN


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MHC-Binding
Epitope  
   
Complex PDB ID 1BX2
Accession Number 3DIEP0396
IEDB ID 13572
Epitope Sequence ENPVVHFFKNIVTPR
Starting Position86
Ending Position99
Epitope Type Linear Epitope

Assay Information  
Assay Antigen Purified MHC - X-ray crystallography Structure (crystal; NMR; etc.)
PDB CategoryIMMUNE SYSTEM
Keyword HLA-DR2; MYELIN BASIC PROTEIN; MULTIPLE SCLEROSIS; AUTOIMMUNITY; IMMUNE SYSTEM
Antibody Residues Interacting with Antigen Open in new window      Download dimplot pdb file
Antibody Chain 1 PDB Chain D
Antigen PDB ChainF
CommentsThere are two molecules in the asymmetric unit of the crystal. The first MHC molecule (chains D; E) is complexed with epitope residues 86-99 (chain F) and the second MHC (chains A; B) with epitope residues 85-98 (chain C). Hereafter; complex ABC is denoted complex I and complex DEF is denoted complex II. A crystal contact between the peptide residue P-3 in the complex I and P5 from the complex II stabilizes the NH2 terminus of the peptide in the complex I; enabling P-4 to be included in the model for the complex I and P5 to be included in the model for the complex II. The two non-crystallographically related epitope peptides have slightly different conformation of epitope residues P6 to P10; because of different crystal contacts to the MHC ?-helix. Specifically; for one molecule in the asymmetric unit there is a crystal contact of A: R50 on a symmetry related molecule with B: D66; Q64; Y60; and P6 residue I.

Experimental Details
Method
X-RAY DIFFRACTION
Resolution
2.6
R-Value
0.238
Space Group
P 43 21 2
Unit Cell
Length(Å) Angle(°)
a = 95.403 α = 90
b = 95.403 β = 90
c = 295.219 γ = 90


Source Information  
Structure Determination Method X-RAY DIFFRACTION
Source Organism Homo sapiens
Common Namehuman
Taxonomic ID9606
Source Organism Homo sapiens
Common Namehuman
Taxonomic ID9606
Entity ID3
Host Organismunidentified baculovirus
Host Taxonomic ID 10469
Host Orgism VectorBACULOVIRUS
Host Orgism Vector Type BACULOVIRUS

Ligand non-polymer
 
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,D
Source Method
genetically manipulated
Molecule Name
PROTEIN (HLA-DR2)
Fragment Name
EXTRACELLULAR DOMAINS ALPHA 1, ALPHA 2
Sequence Length
180

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,E
Source Method
Natural
Molecule Name
PROTEIN (HLA-DR2)
Fragment Name
EXTRACELLULAR DOMAINS BETA 1, BETA 2
Sequence Length
191

T R P R F L W Q P K R E C H F F N G T E R V R F L D R Y F Y N Q E E S V R F D S D V G E F R A V T E L G R P D A E Y W N S Q K D I L E Q A R A A V D T Y C R H N Y G V V E S F T V Q R R V Q P K V T V Y P S K T Q P L Q H H N L L V C S V S G F Y P G S I E V R W F L N G Q E E K A G M 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 E
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
Natural
Molecule Name
PROTEIN (HLA-DR2)
Fragment Name
PEPTIDE FROM HUMAN MYELIN BASIC PROTEIN
Sequence Length
15

E N P V V H F F K N I V T P R
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)

X-RAY DIFFRACTION

Crystalization

pH
3.5
pH details
15-18% PEG6000 100MM GLYCINE PH3.5


Crystal Data
Unit Cell
Space group
P 43 21 2
Length
Angle
°
a  =
95.403
α  =
90
b  =
95.403
β  =
90
c  =
295.219
γ  =
90


Diffraction
Diffraction Detector
Diffraction radiation
Detector
CCD
Monochromator
Type
CHESS BEAMLINE A1
Diffraction Source
Detail
Source
SYNCHROTRON
Collection date
3/18/1998
Type
CHESS BEAMLINE A1


Refinement Data
Reflection Details
Structure Solution Method
MOLECULAR REPLACEMENT
Percent Possible(Observed)
87.9
Resolution(High)
2.6
R-Factor(Observed)
0.238
Cut-off Sigma(F)
2
R-Work
0.238
Number Reflections(Observed)
37678
R-Free
No. of Non-Hydrogen atoms
Used in Refinement
Protein atom
6230
Nucleic acid atom
Heterogen Atoms
Solvent Atoms
50
Total Atoms
6280


Software and Computing
Computing
Software
Data Reduction (intensity integration)
DENZO
model building
Data Reduction (data scaling)
SCALEPACK
refinement
X-PLOR 3.851
Structure Solution
AMORE
Structure Refinement
X-PLOR 3.851

GO functional annotation for 1bx2

  Cellular component Chain(s)
  0016020  
  membrane
A, B, D, E 
  0042613  
    MHC class II protein complex
A, B, D, E 
  Biological process Chain(s)
  0006955  
  immune response
A, B, D, E 
  0019882  
  antigen processing and presentation
A, B, D, E 
  Biochemical function Chain(s)
  0019911  
  structural constituent of myelin sheath
C, F 


Literature reference

Title
Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein.
Authors
Journal
Year
Journal Volume
First Page
Last Page
PubMed Abstract
Susceptibility to multiple sclerosis is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 (DRB1*1501) haplotype. The structure of HLA-DR2 was determined with a bound peptide from human myelin basic protein (MBP) that is immunodominant for human MBP-specific T cells. Residues of MBP peptide that are important for T cell receptor recognition are prominent; solvent exposed residues in the crystal structure. A distinguishing feature of the HLA-DR2 peptide binding site is a large; primarily hydrophobic P4 pocket that accommodates a phenylalanine of the MBP peptide. The necessary space for this aromatic side chain is created by an alanine at the polymorphic DRbeta 71 position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules associated with other autoimmune diseases.
PubMed ID
Search related article in PubMed
Keywords
HLA-DR2; MYELIN BASIC PROTEIN; MULTIPLE SCLEROSIS; AUTOIMMUNITY; IMMUNE SYSTEM




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Ag-Ab Interaction of the1BX2 between chain "F" and chain "D"



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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.