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PDBsum entry 1lk3
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protein Protein-protein interface(s) links
Immune system PDB id
1lk3

 

 

 

 

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Contents
Protein chains
136 a.a. *
210 a.a. *
219 a.a. *
Waters ×1203
* Residue conservation analysis
PDB id:
1lk3
Name: Immune system
Title: Engineered human interleukin-10 monomer complexed to 9d7 fab fragment
Structure: Interleukin-10. Chain: a, b. Fragment: residues 26-175. Synonym: il-10m1 (engineered monomer of human interleukin-10), il-10, cytokine synthesis inhibitory factor, csif. Engineered: yes. 9d7 light chain. Chain: l, m. Fragment: fab fragment, residues 1-210.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: il10. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Rattus norvegicus. Norway rat. Organism_taxid: 10116.
Biol. unit: Trimer (from PQS)
Resolution:
1.91Å     R-factor:   0.187     R-free:   0.240
Authors: K.Josephson,B.C.Jones,L.J.Walter,R.Digiacomo,S.R.Indelicato, M.R.Walter
Key ref:
K.Josephson et al. (2002). Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and x-ray crystallography. Structure, 10, 981-987. PubMed id: 12121653 DOI: 10.1016/S0969-2126(02)00791-8
Date:
23-Apr-02     Release date:   17-Jul-02    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P22301  (IL10_HUMAN) -  Interleukin-10 from Homo sapiens
Seq:
Struc: 		178 a.a.
136 a.a.
Protein chains
Pfam   ArchSchema ?
P01835  (KACB_RAT) -  Ig kappa chain C region, B allele from Rattus norvegicus
Seq:
Struc: 		106 a.a.
210 a.a.
Protein chains
Pfam   ArchSchema ?
P20759  (IGHG1_RAT) -  Ig gamma-1 chain C region from Rattus norvegicus
Seq:
Struc: 		326 a.a.
219 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/S0969-2126(02)00791-8 Structure 10:981-987 (2002)
PubMed id: 12121653  
 
 
Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and x-ray crystallography.
K.Josephson, B.C.Jones, L.J.Walter, R.DiGiacomo, S.R.Indelicato, M.R.Walter.
 
  ABSTRACT  
 
IL-10 is a dimeric cytokine that must engage its high-affinity cell surface receptor, IL-10R1, to induce multiple cellular activities. Here we report the 1.9 A crystal structure of an engineered IL-10 monomer (IL-10M1) in complex with a neutralizing Fab fragment (9D7Fab). 9D7Fab and IL-10R1 bind distinct nonoverlapping surfaces on IL-10M1. Antagonism of the IL-10M1/IL-10R1 interaction is the result of 9D7Fab-induced conformational changes in the CD loop of IL-10M1 that indirectly alter the structure of the IL-10R1 binding site. A single mutation (Ile87Ala) in the same CD loop region of the Epstein-Barr virus IL-10 (ebvIL-10) also reduces IL-10R1 binding affinity, suggesting that ebvIL-10 and 9D7Fab use similar allosteric mechanisms to modulate IL-10R1 affinity and biological activity.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The IL-10M1/9D7Fab Complex and Interface(A) Ribbon diagram of the IL-10M1/9D7Fab complex with IL-10M1 in orange and the 9D7Fab heavy and light chains in red and blue, respectively. The 9D7Fab epitope, residues 71-83 and 125-137, is in green.(B) Stereo diagram of the IL-10M1/9D7Fab interface colored as described in panel A. Nitrogen atoms, blue; oxygen atoms, red; interfacial waters, magenta spheres; hydrogen bonds, dashed black lines.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 981-987) copyright 2002.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20846897 A.Zdanov (2010).
Structural analysis of cytokines comprising the IL-10 family.
  Cytokine Growth Factor Rev, 21, 325-330.  
19776018 I.C.Wilkinson, C.J.Hall, V.Veverka, J.Y.Shi, F.W.Muskett, P.E.Stephens, R.J.Taylor, A.J.Henry, and M.D.Carr (2009).
High resolution NMR-based model for the structure of a scFv-IL-1beta complex: potential for NMR as a key tool in therapeutic antibody design and development.
  J Biol Chem, 284, 31928-31935.
PDB code: 2kh2
17224278 S.I.Yoon, and M.R.Walter (2007).
Identification and characterization of a +1 frameshift observed during the expression of Epstein-Barr virus IL-10 in Escherichia coli.
  Protein Expr Purif, 53, 132-137.  
16982608 S.I.Yoon, N.J.Logsdon, F.Sheikh, R.P.Donnelly, and M.R.Walter (2006).
Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex.
  J Biol Chem, 281, 35088-35096.
PDB code: 2h24
15837194 S.I.Yoon, B.C.Jones, N.J.Logsdon, and M.R.Walter (2005).
Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain.
  Structure, 13, 551-564.
PDB codes: 1y6k 1y6m 1y6n
15032600 S.Pestka, C.D.Krause, D.Sarkar, M.R.Walter, Y.Shi, and P.B.Fisher (2004).
Interleukin-10 and related cytokines and receptors.
  Annu Rev Immunol, 22, 929-979.  
12403790 C.Chang, E.Magracheva, S.Kozlov, S.Fong, G.Tobin, S.Kotenko, A.Wlodawer, and A.Zdanov (2003).
Crystal structure of interleukin-19 defines a new subfamily of helical cytokines.
  J Biol Chem, 278, 3308-3313.
PDB code: 1n1f
12513909 N.J.Logsdon, B.C.Jones, K.Josephson, J.Cook, and M.R.Walter (2002).
Comparison of interleukin-22 and interleukin-10 soluble receptor complexes.
  J Interferon Cytokine Res, 22, 1099-1112.  
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 code is shown on the right.

 

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