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PDBsum entry 4fqx

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protein ligands links
Immune system PDB id
4fqx
Jmol
Contents
Protein chains
186 a.a.
191 a.a.
180 a.a.
187 a.a.
Ligands
ASN-CYS-LEU-LYS-
LEU-ALA-THR
NAG-NAG
Waters ×124
PDB id:
4fqx
Name: Immune system
Title: Crystal structure of hla-dm bound to hla-dr1
Structure: Hla class ii histocompatibility antigen, dm alpha chain: c. Fragment: unp residues 27-225. Synonym: mhc class ii antigen dma, really interesting new g protein. Engineered: yes. Hla class ii histocompatibility antigen, dm beta chain: d. Fragment: unp residues 19-211.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: dm alpha chain, dma, hla class ii histocompatibility hla-dma, ring6. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: dm beta chain, dmb, hla class ii histocompatibility a hla-dmb, ring7.
Resolution:
2.60Å     R-factor:   0.196     R-free:   0.240
Authors: D.K.Sethi,W.Pos,K.W.Wucherpfennig
Key ref: W.Pos et al. (2012). Crystal structure of the HLA-DM-HLA-DR1 complex defines mechanisms for rapid peptide selection. Cell, 151, 1557-1568. PubMed id: 23260142 DOI: 10.1016/j.cell.2012.11.025
Date:
25-Jun-12     Release date:   09-Jan-13    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28067  (DMA_HUMAN) -  HLA class II histocompatibility antigen, DM alpha chain
Seq:
Struc:
261 a.a.
186 a.a.*
Protein chain
Pfam   ArchSchema ?
P28068  (DMB_HUMAN) -  HLA class II histocompatibility antigen, DM beta chain
Seq:
Struc:
263 a.a.
191 a.a.*
Protein chain
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
Seq:
Struc:
254 a.a.
180 a.a.*
Protein chain
Pfam   ArchSchema ?
P04229  (2B11_HUMAN) -  HLA class II histocompatibility antigen, DRB1-1 beta chain
Seq:
Struc:
266 a.a.
187 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 14 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     immune response   2 terms 

 

 
DOI no: 10.1016/j.cell.2012.11.025 Cell 151:1557-1568 (2012)
PubMed id: 23260142  
 
 
Crystal structure of the HLA-DM-HLA-DR1 complex defines mechanisms for rapid peptide selection.
W.Pos, D.K.Sethi, M.J.Call, M.S.Schulze, A.K.Anders, J.Pyrdol, K.W.Wucherpfennig.
 
  ABSTRACT  
 
HLA-DR molecules bind microbial peptides in an endosomal compartment and present them on the cell surface for CD4 T cell surveillance. HLA-DM plays a critical role in the endosomal peptide selection process. The structure of the HLA-DM-HLA-DR complex shows major rearrangements of the HLA-DR peptide-binding groove. Flipping of a tryptophan away from the HLA-DR1 P1 pocket enables major conformational changes that position hydrophobic HLA-DR residues into the P1 pocket. These conformational changes accelerate peptide dissociation and stabilize the empty HLA-DR peptide-binding groove. Initially, incoming peptides have access to only part of the HLA-DR groove and need to compete with HLA-DR residues for access to the P2 site and the hydrophobic P1 pocket. This energetic barrier creates a rapid and stringent selection process for the highest-affinity binders. Insertion of peptide residues into the P2 and P1 sites reverses the conformational changes, terminating selection through DM dissociation.