HLA-DR1 (DRA; DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE


Tab-View Sample


MHC-Binding
Epitope  
   
Complex PDB ID 1AQD
Accession Number 3DIEP0398
IEDB ID 68791
Epitope Sequence VGSDWRFLRGYHQYA
Starting Position2
Ending Position15
Epitope Type Linear Epitope

Assay Information  
Assay Antigen "Purified MHC - X-ray crystallography Structure (crystal; NMR; etc.)"
PDB CategoryCOMPLEX (MHC PROTEIN/ANTIGEN)
Keyword COMPLEX (MHC PROTEIN/ANTIGEN); HISTOCOMPATIBILITY ANTIGEN
Antibody Residues Interacting with Antigen Open in new window      Download dimplot pdb file
Antibody Chain 1 PDB Chain G
Antigen PDB ChainI
CommentsThe asymmetric unit contains four molecules. Each one has a HLA-DR1 dimer complexed with the epitope peptide. The four complexes are arranged as two copies of essentially the same (ab)2 dimer: complex I: ?-chain A; ?-chain B; peptide C; complex II: ?-chain D; ?-chain E; peptide F; complex III: ?-chain G; ?-chain H; peptide I; complex IV: ?-chain J; ?-chain K; peptide L. Complex III is the most well defined. The first epitope residue (V1) is disordered in all four complexes and coordinates are not included in the model. Complexes I; III and IV contain the same residues in each chain and complex II is also missing the second epitope residue (G2). Since complex III is the most well defined; it has the best model. Thus; it will be the only one curated.The sidechain of epitope residue P7: Y11 is found in two different orientations in different complexes in the asymmetric unit.Water molecules were added in the model based on outputs from the CCP4 suite of programs and ARP. There are three water molecules underneath the peptide in the region between pockets 6 and 7; which form a network that is variously occupied in the four complexes.

Experimental Details
Method
X-RAY DIFFRACTION
Resolution
2.45
R-Value
0.216
Space Group
C 1 2 1
Unit Cell
Length(Å) Angle(°)
a = 134.514 α = 90
b = 134.32 β = 104.82
c = 131.232 γ = 90


Source Information  
Structure Determination Method X-RAY DIFFRACTION
Host OrganismSpodoptera frugiperda
Host Taxonomic ID 7108
Host Orgism VectorPVL1392-BASED
Host Orgism Vector Type PVL1392-BASED

Ligand non-polymer
 

Sequence


Protein Name
HLA-DR1 (DRA; DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE
Poly type
polypeptide(L)
Sequence status
Complete

Primary Sequence

Entity ID
1
Chain ID
A,D,G,J
Source Method
genetically manipulated
Molecule Name
HLA-DR1 CLASS II HISTOCOMPATIBILITY PROTEIN
Fragment Name
SECRETED EXTRACELLULAR DOMAINS
Sequence Length
192

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 A P S P L P E T T E N
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)
Primary Sequence

Entity ID
2
Chain ID
B,E,H,K
Source Method
genetically manipulated
Molecule Name
HLA-DR1 CLASS II HISTOCOMPATIBILITY PROTEIN
Fragment Name
SECRETED EXTRACELLULAR DOMAINS
Sequence Length
198

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

Entity ID
3
Chain ID
C,F,I,L
Source Method
genetically manipulated
Molecule Name
HLA-A2
Fragment Name
ANTIGENIC PEPTIDE
Sequence Length
15

V G S D W R F L R G Y H Q Y A
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)

X-RAY DIFFRACTION

Crystalization

pH
3.5
pH details
CRYSTALS GREW AS NEEDLES FROM 10MG/ML HLA-DR1 / PEPTIDE COMPLEX, 15% PEG 4000, 100MM GLYCINE, PH 3.5, AT ROOM TEMPERATURE, OVER ONE WEEK.


Crystal Data
Unit Cell
Space group
C 1 2 1
Length
Angle
°
a  =
134.514
α  =
90
b  =
134.32
β  =
104.82
c  =
131.232
γ  =
90


Diffraction
Diffraction Detector
Diffraction radiation
Detector
IMAGE PLATE
Monochromator
Type
CHESS BEAMLINE F1
Diffraction Source
Detail
Source
SYNCHROTRON
Collection date
1995-02
Type
CHESS BEAMLINE F1


Refinement Data
Reflection Details
Structure Solution Method
MOLECULAR REPLACEMENT
Percent Possible(Observed)
89
Resolution(High)
2.45
R-Factor(Observed)
0.216
Cut-off Sigma(F)
2
R-Work
0.216
Number Reflections(Observed)
68842
R-Free
No. of Non-Hydrogen atoms
Used in Refinement
Protein atom
11867
Nucleic acid atom
0
Heterogen Atoms
0
Solvent Atoms
152
Total Atoms
12019


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 3.1
Structure Refinement
X-PLOR 3.1

GO functional annotation for 1aqd



Literature reference

Title
The class II MHC protein HLA-DR1 in complex with an endogenous peptide: implications for the structural basis of the specificity of peptide binding.
Authors
Journal
Year
Journal Volume
First Page
Last Page
PubMed Abstract
BACKGROUND: Class II major histocompatibility complex (MHC) proteins are cell surface glycoproteins that bind peptides and present them to T cells as part of the mechanism for detecting and responding to foreign material in the body. The peptide-binding activity exhibits allele-specific preferences for particular sidechains at some positions; although the structural basis of these preferences is not understood in detail. We have determined the 2.45 A crystal structure of the human class II MHC protein HLA-DR1 in complex with the tight binding endogenous peptide A2 (103-117) in order to discover peptide-MHC interactions that are important in determining the binding motif and to investigate conformational constraints on the bound peptide. RESULTS: The bound peptide adopts a polyproline II-like conformation and places several sidechains within pockets in the binding site. Bound water molecules mediate MHC-peptide contacts at several sites. A tryptophan residue from the beta 2 'lower' domain of HLA-DR1 was found to project into a pocket underneath the peptide-binding domain and may be important in modulating interdomain interactions in MHC proteins. CONCLUSIONS: The peptide-binding motif of HLA-DR1 includes an aromatic residue at position +1; an arginine residue at position +2; and a small residue at position +6 (where the numbering refers to the normal MHC class II convention); these preferences can be understood in light of interactions observed in the peptide-MHC complex. Comparison of the structure with that of another MHC-peptide complex shows that completely different peptide sequences bind in essentially the same conformation and are accommodated with only minimal rearrangement of HLA-DR1 residues. Small conformational differences that are observed appear to be important in interactions with other proteins.
PubMed ID
Search related article in PubMed
Keywords
COMPLEX (MHC PROTEIN/ANTIGEN); HISTOCOMPATIBILITY ANTIGEN




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Ag-Ab Interaction of the1AQD between chain "I" and chain "G"



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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.