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Immune system PDB id
1lqs
Jmol
Contents
Protein chains
207 a.a. *
142 a.a. *
Ligands
NAG ×2
Waters ×48
* Residue conservation analysis
PDB id:
1lqs
Name: Immune system
Title: Crystal structure of human cytomegalovirus il-10 bound to so human il-10r1
Structure: Interleukin-10 receptor alpha chain. Chain: r, s. Fragment: extracellular domain, residues 22-235. Synonym: il-10r-a, il-10r1. Engineered: yes. Mutation: yes. Interleukin-10-like protein. Chain: l, m. Fragment: residues 20-176.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Human herpesvirus 5. Human cytomegalovirus. Organism_taxid: 10359.
Biol. unit: Octamer (from PQS)
Resolution:
2.70Å     R-factor:   0.244     R-free:   0.294
Authors: B.C.Jones,N.J.Logsdon,K.Josephson,J.Cook,P.A.Barry,M.R.Walte
Key ref:
B.C.Jones et al. (2002). Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1. Proc Natl Acad Sci U S A, 99, 9404-9409. PubMed id: 12093920 DOI: 10.1073/pnas.152147499
Date:
13-May-02     Release date:   17-Jul-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q13651  (I10R1_HUMAN) -  Interleukin-10 receptor subunit alpha
Seq:
Struc: 		 
Seq:
Struc: 		578 a.a.
207 a.a.*
Protein chains
Pfam   ArchSchema ?
P17150  (IL10H_HCMVA) -  Viral interleukin-10 homolog
Seq:
Struc: 		175 a.a.
142 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     immune response   3 terms 
  Biochemical function     protein binding     2 terms  

 

 
DOI no: 10.1073/pnas.152147499 Proc Natl Acad Sci U S A 99:9404-9409 (2002)
PubMed id: 12093920  
 
 
Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1.
B.C.Jones, N.J.Logsdon, K.Josephson, J.Cook, P.A.Barry, M.R.Walter.
 
  ABSTRACT  
 
Human IL-10 (hIL-10) modulates critical immune and inflammatory responses by way of interactions with its high- (IL-10R1) and low-affinity (IL-10R2) cell surface receptors. Human cytomegalovirus exploits the IL-10 signaling pathway by expressing a functional viral IL-10 homolog (cmvIL-10), which shares only 27% sequence identity with hIL-10 yet signals through IL-10R1 and IL-10R2. To define the molecular basis of this virus-host interaction, we determined the 2.7-A crystal structure of cmvIL-10 bound to the extracellular fragment of IL-10R1 (sIL-10R1). The structure reveals cmvIL-10 forms a disulfide-linked homodimer that binds two sIL-10R1 molecules. Although cmvIL-10 and hIL-10 share similar intertwined topologies and sIL-10R1 binding sites, their respective interdomain angles differ by approximately 40 degrees. This difference results in a striking re-organization of the IL-10R1s in the putative cell surface complex. Solution binding studies show cmvIL-10 and hIL-10 share essentially identical affinities for sIL-10R1 whereas the Epstein-Barr virus IL-10 homolog (ebvIL-10), whose structure is highly similar to hIL-10, exhibits a approximately 20-fold reduction in sIL-10R1 affinity. Our results suggest cmvIL-10 and ebvIL-10 have evolved different molecular mechanisms to engage the IL-10 receptors that ultimately enhance the respective ability of their virus to escape immune detection.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. The sIL-10R1 binding epitope. cmvIL-10 and hIL-10 scaffold residues (10-62 and 137-157 for cmvIL-10, 11-62 and 137-160 for hIL-10) are shown in green and blue, respectively. cmvIL-10 residues that bury surface area into sIL-10R1 are shown in red whereas hIL-10 residues are yellow. Side chains are shown for conserved side chain residues that bury surface area into each interface. 		Figure 4.
Fig. 4. Stereoview of conformational changes in cmvIL-10 and hIL-10 Site Ia interfaces. cmvIL-10 and hIL-10 residues are shown in cyan and magenta, respectively. sIL-10R1 residues Tyr-43, Arg-76, and Arg-96 are colored yellow in the cmvIL-10/sIL-10R1 complex and green in the hIL-10/sIL-10R1 complex. The second conformation of sIL-10R1 Arg-76 in the hIL-10/sIL-10R1 is not shown for clarity but adopts the same conformation as sIL-10R1 Arg-76 bound to cmvIL-10 (yellow).
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21345680 N.T.Doncheva, K.Klein, F.S.Domingues, and M.Albrecht (2011).
Analyzing and visualizing residue networks of protein structures.
  Trends Biochem Sci, 36, 179-182.  
20846897 A.Zdanov (2010).
Structural analysis of cytokines comprising the IL-10 family.
  Cytokine Growth Factor Rev, 21, 325-330.  
20521934 B.Slobedman, J.Z.Cao, S.Avdic, B.Webster, S.McAllery, A.K.Cheung, J.C.Tan, and A.Abendroth (2010).
Human cytomegalovirus latent infection and associated viral gene expression.
  Future Microbiol, 5, 883-900.  
20454917 D.B.Trivella, J.R.Ferreira-Júnior, L.Dumoutier, J.C.Renauld, and I.Polikarpov (2010).
Structure and function of interleukin-22 and other members of the interleukin-10 family.
  Cell Mol Life Sci, 67, 2909-2935.  
20462497 S.I.Yoon, B.C.Jones, N.J.Logsdon, B.D.Harris, A.Deshpande, S.Radaeva, B.A.Halloran, B.Gao, and M.R.Walter (2010).
Structure and mechanism of receptor sharing by the IL-10R2 common chain.
  Structure, 18, 638-648.
PDB code: 3lqm
21149711 W.L.Chang, and P.A.Barry (2010).
Attenuation of innate immunity by cytomegalovirus IL-10 establishes a long-term deficit of adaptive antiviral immunity.
  Proc Natl Acad Sci U S A, 107, 22647-22652.  
19640997 B.Slobedman, P.A.Barry, J.V.Spencer, S.Avdic, and A.Abendroth (2009).
Virus-encoded homologs of cellular interleukin-10 and their control of host immune function.
  J Virol, 83, 9618-9629.  
19734147 K.L.Fuson, M.Zheng, M.Craxton, A.Pataer, R.Ramesh, S.Chada, and R.B.Sutton (2009).
Structural mapping of post-translational modifications in human interleukin-24: role of N-linked glycosylation and disulfide bonds in secretion and activity.
  J Biol Chem, 284, 30526-30533.  
  19134204 M.Miller-Kittrell, and T.E.Sparer (2009).
Feeling manipulated: cytomegalovirus immune manipulation.
  Virol J, 6, 4.  
19142637 M.Terai, Y.Tamura, V.Alexeev, E.Ohtsuka, D.Berd, M.J.Mastrangelo, and T.Sato (2009).
Human interleukin 10 receptor 1/IgG1-Fc fusion proteins: immunoadhesins for human IL-10 with therapeutic potential.
  Cancer Immunol Immunother, 58, 1307-1317.  
19038442 S.M.van Putten, M.Wübben, W.E.Hennink, M.J.van Luyn, and M.C.Harmsen (2009).
The downmodulation of the foreign body reaction by cytomegalovirus encoded interleukin-10.
  Biomaterials, 30, 730-735.  
18216121 C.Jenkins, W.Garcia, M.J.Godwin, J.V.Spencer, J.L.Stern, A.Abendroth, and B.Slobedman (2008).
Immunomodulatory properties of a viral homolog of human interleukin-10 expressed by human cytomegalovirus during the latent phase of infection.
  J Virol, 82, 3736-3750.  
18086805 J.J.Lazarus, M.A.Kay, A.L.McCarter, and R.M.Wooten (2008).
Viable Borrelia burgdorferi enhances interleukin-10 production and suppresses activation of murine macrophages.
  Infect Immun, 76, 1153-1162.  
19115937 J.Nachtwey, and J.V.Spencer (2008).
HCMV IL-10 suppresses cytokine expression in monocytes through inhibition of nuclear factor-kappaB.
  Viral Immunol, 21, 477-482.  
18222515 J.V.Spencer, J.Cadaoas, P.R.Castillo, V.Saini, and B.Slobedman (2008).
Stimulation of B lymphocytes by cmvIL-10 but not LAcmvIL-10.
  Virology, 374, 164-169.  
19016528 S.G.Gruber, M.Gloria Luciani, P.Grundtner, A.Zdanov, and C.Gasche (2008).
Differential signaling of cmvIL-10 through common variants of the IL-10 receptor 1.
  Eur J Immunol, 38, 3365-3375.  
17976852 Y.L.Lin, P.C.Chang, Y.Wang, and M.Li (2008).
Identification of novel viral interleukin-10 isoforms of human cytomegalovirus AD169.
  Virus Res, 131, 213-223.  
17066477 A.Schosser, H.N.Aschauer, D.B.Wildenauer, S.G.Schwab, M.Albus, W.Maier, M.Schloegelhofer, F.Leisch, K.Hornik, S.S.Murray, and C.Gasche (2007).
Homozygosity of the interleukin-10 receptor 1 G330R allele is associated with schizophrenia.
  Am J Med Genet B Neuropsychiatr Genet, 144, 347-350.  
17121792 J.V.Spencer (2007).
The cytomegalovirus homolog of interleukin-10 requires phosphatidylinositol 3-kinase activity for inhibition of cytokine synthesis in monocytes.
  J Virol, 81, 2083-2086.  
16553554 S.Pepperl-Klindworth, K.Besold, N.Frankenberg, M.Farkas, J.Kuball, M.Theobald, and B.Plachter (2006).
Cytomegalovirus interleukin-10 expression in infected cells does not impair MHC class I restricted peptide presentation on bystanding antigen-presenting cells.
  Viral Immunol, 19, 92.  
15817386 L.Pereira, E.Maidji, S.McDonagh, and T.Tabata (2005).
Insights into viral transmission at the uterine-placental interface.
  Trends Microbiol, 13, 164-174.  
16007103 S.Giebel, R.Maccario, D.Lilleri, M.Zecca, M.A.Avanzini, M.Marconi, A.Di Cesare Merlone, G.Campanini, D.Montagna, P.Travaglino, R.Gentile, S.Telli, D.Pagliara, J.Holowiecki, and F.Locatelli (2005).
The immunosuppressive effect of human cytomegalovirus infection in recipients of allogeneic hematopoietic stem cell transplantation.
  Bone Marrow Transplant, 36, 503-509.  
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
15985167 S.Pletnev, E.Magracheva, A.Wlodawer, and A.Zdanov (2005).
A model of the ternary complex of interleukin-10 with its soluble receptors.
  BMC Struct Biol, 5, 10.  
  14746812 J.A.Langer, E.C.Cutrone, and S.Kotenko (2004).
The Class II cytokine receptor (CRF2) family: overview and patterns of receptor-ligand interactions.
  Cytokine Growth Factor Rev, 15, 33-48.  
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.  
14990702 T.Yamamoto-Tabata, S.McDonagh, H.T.Chang, S.Fisher, and L.Pereira (2004).
Human cytomegalovirus interleukin-10 downregulates metalloproteinase activity and impairs endothelial cell migration and placental cytotrophoblast invasiveness in vitro.
  J Virol, 78, 2831-2840.  
15280480 W.L.Chang, N.Baumgarth, D.Yu, and P.A.Barry (2004).
Human cytomegalovirus-encoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality.
  J Virol, 78, 8720-8731.  
12663757 M.C.Cheeran, S.Hu, W.S.Sheng, P.K.Peterson, and J.R.Lokensgard (2003).
CXCL10 production from cytomegalovirus-stimulated microglia is regulated by both human and viral interleukin-10.
  J Virol, 77, 4502-4515.  
14732928 R.L.Rich, and D.G.Myszka (2003).
A survey of the year 2002 commercial optical biosensor literature.
  J Mol Recognit, 16, 351-382.  
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.