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PDBsum entry 3iu3

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protein ligands Protein-protein interface(s) links
Immune system PDB id
3iu3
Jmol
Contents
Protein chains
215 a.a.
208 a.a. *
119 a.a. *
116 a.a. *
Ligands
NAG-NAG-BMA ×3
* Residue conservation analysis
PDB id:
3iu3
Name: Immune system
Title: Crystal structure of the fab fragment of therapeutic antibod basiliximab in complex with il-2ra (cd25) ectodomain
Structure: Heavy chain of fab fragment of basiliximab. Chain: a, c, h. Engineered: yes. Light chain of fab fragment of basiliximab. Chain: b, d, l. Engineered: yes. Interleukin-2 receptor alpha chain. Chain: i, j, k. Fragment: extracellular domain, ectodomain, unp residues 22
Source: Mus musculus, homo sapiens. Mouse, human. Organism_taxid: 10090, 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: il-2ra.
Resolution:
2.90Å     R-factor:   0.217     R-free:   0.262
Authors: J.Du,H.Yang,J.Wang,J.Ding
Key ref: J.Du et al. (2010). Structural basis for the blockage of IL-2 signaling by therapeutic antibody basiliximab. J Immunol, 184, 1361-1368. PubMed id: 20032294 DOI: 10.4049/jimmunol.0903178
Date:
29-Aug-09     Release date:   26-Jan-10    
PROCHECK
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 Headers
 References

Protein chains
No UniProt id for this chain
Struc: 215 a.a.
Protein chains
Pfam   ArchSchema ?
P01834  (IGKC_HUMAN) -  Ig kappa chain C region
Seq:
Struc:
106 a.a.
208 a.a.
Protein chains
Pfam   ArchSchema ?
P01589  (IL2RA_HUMAN) -  Interleukin-2 receptor subunit alpha
Seq:
Struc:
272 a.a.
119 a.a.
Protein chain
Pfam   ArchSchema ?
P01589  (IL2RA_HUMAN) -  Interleukin-2 receptor subunit alpha
Seq:
Struc:
272 a.a.
116 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   5 terms 
  Biological process     Fc-epsilon receptor signaling pathway   8 terms 
  Biochemical function     antigen binding     1 term  

 

 
DOI no: 10.4049/jimmunol.0903178 J Immunol 184:1361-1368 (2010)
PubMed id: 20032294  
 
 
Structural basis for the blockage of IL-2 signaling by therapeutic antibody basiliximab.
J.Du, H.Yang, D.Zhang, J.Wang, H.Guo, B.Peng, Y.Guo, J.Ding.
 
  ABSTRACT  
 
IL-2 signaling plays a central role in the initiation and activation of immune responses. Correspondingly, blockage of this pathway leads to inhibition of the immune system and would provide some therapeutic benefits. Basiliximab (Simulect), a therapeutic mAb drug with specificity against IL-2R alpha of T cells, was approved by U.S. Food and Drug Administration in 1998. It has been proven to be effective in the suppression of the IL-2 pathway and hence has been widely used to prevent allograft rejection in organ transplantation, especially in kidney transplants. In this study, we report the crystal structure of the basiliximab Fab in complex with the ectodomain of IL-2R alpha at 2.9 A resolution. In the complex structure, the Fab interacts with IL-2R alpha with extensive hydrophobic and hydrophilic interactions, accounting for a high binding affinity of 0.14 nM. The Ag binding site of basiliximab consists of all six CDR loops that form a large binding interface with a central shallow hydrophobic groove surrounded by four hydrophilic patches. The discontinuous epitope is composed of several segments from the D1 domain and a minor segment from the D2 domain that overlap with most of the regions responsible for the interactions with IL-2. Thus, basiliximab binding can completely block the interactions of IL-2 with IL-2R alpha and hence inhibit the activation of the IL-2 signal pathway. The structural results also provide important implications for the development of improved and new IL-2R alpha-targeted mAb drugs.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21475065 S.Heidt, S.Shankar, A.S.Muthusamy, D.San Segundo, and K.J.Wood (2011).
Pretransplant serum CXCL9 and CXCL10 levels fail to predict acute rejection in kidney transplant recipients receiving induction therapy.
  Transplantation, 91, e59-e61.  
20820193 H.Yang, J.Wang, J.Du, C.Zhong, D.Zhang, H.Guo, Y.Guo, and J.Ding (2010).
Structural basis of immunosuppression by the therapeutic antibody daclizumab.
  Cell Res, 20, 1361-1371.
PDB codes: 3nfp 3nfs
20689592 M.G.de Goër de Herve, E.Gonzales, H.Hendel-Chavez, J.L.Décline, O.Mourier, K.Abbed, E.Jacquemin, and Y.Taoufik (2010).
CD25 appears non essential for human peripheral T(reg) maintenance in vivo.
  PLoS One, 5, e11784.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.