3og6

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The crystal structure of human interferon lambda 1 complexed with its high affinity receptor in space group P212121The crystal structure of human interferon lambda 1 complexed with its high affinity receptor in space group P212121

Structural highlights

3og6 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Gene:IFNL1, IL29, ZCYTO21 (HUMAN), hCG_1982865, IL28RA, RP11-10N16.1-001 (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IFNL1_HUMAN] Cytokine with immunomodulatory activity. May play a role in antiviral immunity. Up-regulates MHC class I antigen expression. Ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1. The ligand/receptor complex seems to signal through the Jak-STAT pathway. [INLR1_HUMAN] The IFNLR1/IL10RB dimer is a receptor for IFNL1, IFNL2 and IFNL3. The ligand/receptor complex seems to signal through the Jak-STAT pathway. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium.[1] [2] [3]

Publication Abstract from PubMed

Interferon (IFN)-lambda1 [also known as interleukin (IL)-29] belongs to the recently discovered group of type III IFNs. All type III IFNs initiate signaling processes through formation of specific heterodimeric receptor complexes consisting of IFN-lambdaR1 and IL-10R2. We have determined the structure of human IFN-lambda1 complexed with human IFN-lambdaR1, a receptor unique to type III IFNs. The overall structure of IFN-lambda1 is topologically similar to the structure of IL-10 and other members of the IL-10 family of cytokines. IFN-lambdaR1 consists of two distinct domains having fibronectin type III topology. The ligand-receptor interface includes helix A, loop AB, and helix F on the IFN site, as well as loops primarily from the N-terminal domain and inter-domain hinge region of IFN-lambdaR1. Composition and architecture of the interface that includes only a few direct hydrogen bonds support an idea that long-range ionic interactions between ligand and receptor govern the process of initial recognition of the molecules while hydrophobic interactions finalize it.

Crystal Structure of Human Interferon-lambda1 in Complex with Its High-Affinity Receptor Interferon-lambdaR1.,Miknis Z, Magracheva E, Li W, Zdanov A, Kotenko SV, Wlodawer A J Mol Biol. 2010 Oct 8. PMID:20934432[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Dumoutier L, Lejeune D, Hor S, Fickenscher H, Renauld JC. Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3. Biochem J. 2003 Mar 1;370(Pt 2):391-6. PMID:12521379 doi:10.1042/BJ20021935
  2. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003 Jan;4(1):63-8. Epub 2002 Dec 2. PMID:12469119 doi:10.1038/ni873
  3. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003 Jan;4(1):69-77. Epub 2002 Dec 16. PMID:12483210 doi:10.1038/ni875
  4. Miknis Z, Magracheva E, Li W, Zdanov A, Kotenko SV, Wlodawer A. Crystal Structure of Human Interferon-lambda1 in Complex with Its High-Affinity Receptor Interferon-lambdaR1. J Mol Biol. 2010 Oct 8. PMID:20934432 doi:10.1016/j.jmb.2010.09.068

3og6, resolution 2.10Å

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