PDBsum entry 1y6m

Immune system

PDB id

1y6m

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Contents

			Protein chains

					142 a.a. *


					204 a.a. *

			Waters ×14

* Residue conservation analysis

PDB id:

1y6m

Links

Name:

Immune system

Title:

Crystal structure of epstein-barr virus il-10 complexed with the soluble il-10r1 chain

Structure:

Viral interleukin-10 homolog. Chain: l. Fragment: residues 26-170. Synonym: vil-10, bcrf1 protein, 20 kda protein. Engineered: yes. Interleukin-10 receptor alpha chain. Chain: r. Fragment: extracellular domain, residues 22-235. Synonym: il-10r-a, il-10r1.

Source:

Human herpesvirus 4. Epstein-barr virus. Organism_taxid: 10376. Strain: gd1. Gene: bcrf1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Homo sapiens. Human.

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.80Å

R-factor:

0.261

R-free:

0.315

Authors:

S.I.Yoon,B.C.Jones,N.J.Logsdon,M.R.Walter

Key ref:

S.I.Yoon et al. (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. PubMed id: 15837194 DOI: 10.1016/j.str.2005.01.016

Date:

06-Dec-04

Release date:

03-May-05

PROCHECK

	Headers

	References

Protein chain

P03180 (IL10H_EBVB9) - Viral interleukin-10 homolog from Epstein-Barr virus (strain B95-8)

Seq: Struc:					170 a.a. 142 a.a.

Protein chain

Q13651 (I10R1_HUMAN) - Interleukin-10 receptor subunit alpha from Homo sapiens

Seq: Struc:

Seq: Struc:					578 a.a. 204 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1016/j.str.2005.01.016	Structure 13:551-564 (2005)
PubMed id: 15837194

Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain.
S.I.Yoon, B.C.Jones, N.J.Logsdon, M.R.Walter.

ABSTRACT

Human IL-10 (hIL-10) is a cytokine that modulates diverse immune responses. The Epstein-Barr virus (EBV) genome contains an IL-10 homolog (vIL-10) that shares high sequence and structural similarity with hIL-10. Although vIL-10 suppresses inflammatory responses like hIL-10, it cannot activate many other immunostimulatory functions performed by the cellular cytokine. These functional differences have been correlated with the approximately 1000-fold lower affinity of vIL-10, compared to hIL-10, for the IL-10R1 receptor chain. To define the structural basis for these observations, crystal structures of vIL-10 and a vIL-10 point mutant were determined bound to the soluble IL-10R1 receptor fragment (sIL-10R1) at 2.8 and 2.7 A resolution, respectively. The structures reveal that subtle changes in the conformation and dynamics of the vIL-10 AB and CD loops and an orientation change of vIL-10 on sIL-10R1 are the main factors responsible for vIL-10's reduced affinity for sIL-10R1 and its distinct biological profile.

Selected figure(s)



	Figure 2. Figure 2. Viral and Human IL-10 Orientations and Interdomain Angles (A) hIL-10, (B) vIL-10, and (C) cmvIL-10 dimers bound to sIL-10R1 are shown. The interdomain angles of each IL-10 are shown at the top of each complex. The rotations (in degrees) of each IL-10 domain on the surface of sIL-10R1 are denoted by arrows where the movement is from the circle to the arrowhead. For cmvIL-10/sIL-10R1 complex, the rotation of each sIL-10R1 relative to the hIL-10/sIL-10R1 complex is also shown.

Figure was selected by the author.

Literature references that cite this PDB file's key reference

PubMed id

Reference

22902366

J.Elegheert, N.Bracke, P.Pouliot, I.Gutsche, A.V.Shkumatov, N.Tarbouriech, K.Verstraete, A.Bekaert, W.P.Burmeister, D.I.Svergun, B.N.Lambrecht, B.Vergauwen, and S.N.Savvides (2012).
Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1.

Nat Struct Mol Biol, 19, 938-947.

PDB codes:

3uez 3uf2 3uf5 4adf 4adq

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.

21328379

Y.Chao, Y.Jing, Y.Jia, Y.Wang, C.Zhao, and B.Luo (2011).
Conservation and mutation of viral interleukin-10 gene in gastric carcinomas and nasopharyngeal carcinomas.

J Med Virol, 83, 644-650.

20462488

A.P.Hinck (2010).
Class II cytokine common receptors: something old, something new.

Structure, 18, 551-552.

20846897

A.Zdanov (2010).
Structural analysis of cytokines comprising the IL-10 family.

Cytokine Growth Factor Rev, 21, 325-330.

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

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.

19890111

E.O.Glocker, D.Kotlarz, K.Boztug, E.M.Gertz, A.A.Schäffer, F.Noyan, M.Perro, J.Diestelhorst, A.Allroth, D.Murugan, N.Hätscher, D.Pfeifer, K.W.Sykora, M.Sauer, H.Kreipe, M.Lacher, R.Nustede, C.Woellner, U.Baumann, U.Salzer, S.Koletzko, N.Shah, A.W.Segal, A.Sauerbrey, S.Buderus, S.B.Snapper, B.Grimbacher, and C.Klein (2009).
Inflammatory bowel disease and mutations affecting the interleukin-10 receptor.

N Engl J Med, 361, 2033-2045.

19298643

L.Bortesi, M.Rossato, F.Schuster, N.Raven, J.Stadlmann, L.Avesani, A.Falorni, F.Bazzoni, R.Bock, S.Schillberg, and M.Pezzotti (2009).
Viral and murine interleukin-10 are correctly processed and retain their biological activity when produced in tobacco.

BMC Biotechnol, 9, 22.

18599299

B.C.Jones, N.J.Logsdon, and M.R.Walter (2008).
Structure of IL-22 bound to its high-affinity IL-22R1 chain.

Structure, 16, 1333-1344.

PDB code:

3dgc

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.

18163983

R.D.Irons, and A.T.Le (2008).
Dithiocarbamates and viral IL-10 collaborate in the immortalization and evasion of immune response in EBV-infected human B lymphocytes.

Chem Biol Interact, 172, 81-92.

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.

17763933

K.Kanai, Y.Satoh, H.Yamanaka, A.Kawaguchi, K.Horie, K.Sugata, Y.Hoshikawa, T.Sata, and T.Sairenji (2007).
The vIL-10 gene of the Epstein-Barr virus (EBV) is conserved in a stable manner except for a few point mutations in various EBV isolates.

Virus Genes, 35, 563-569.

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.

17125150

R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.

J Mol Recognit, 19, 478-534.

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

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.