5ixi | pdb_00005ixi

Structure of human JAK1 FERM/SH2 in complex with IFNLR1/IL10RA chimera

Structural highlights

5ixi is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	5ixd
Activity:	Non-specific protein-tyrosine kinase, with EC number 2.7.10.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[JAK1_HUMAN] Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor. [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

JAK1 is a member of the Janus kinase (JAK) family of non-receptor tyrosine kinases that are activated in response to cytokines and interferons. Here, we present two crystal structures of the human JAK1 FERM and SH2 domains bound to peptides derived from the class II cytokine receptors IFN-lambda receptor 1 and IL-10 receptor 1 (IFNLR1 and IL10RA). These structures reveal an interaction site in the JAK1 FERM that accommodates the so-called "box1" membrane-proximal receptor peptide motif. Biophysical analysis of the JAK1-IFNLR1 interaction indicates that the receptor box1 is the primary driver of the JAK1 interaction, and identifies residues conserved among class II receptors as important for binding. In addition, we demonstrate that a second "box2" receptor motif further stabilizes the JAK1-IFNLR1 complex. Together, these data identify a conserved JAK binding site for receptor peptides and elucidate the mechanism by which class II cytokine receptors interact with JAK1.

The Structural Basis for Class II Cytokine Receptor Recognition by JAK1.,Ferrao R, Wallweber HJ, Ho H, Tam C, Franke Y, Quinn J, Lupardus PJ Structure. 2016 Apr 27. pii: S0969-2126(16)30034-X. doi:, 10.1016/j.str.2016.03.023. PMID:27133025^[4]

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

References

↑ 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
↑ 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
↑ 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
↑ Ferrao R, Wallweber HJ, Ho H, Tam C, Franke Y, Quinn J, Lupardus PJ. The Structural Basis for Class II Cytokine Receptor Recognition by JAK1. Structure. 2016 Apr 27. pii: S0969-2126(16)30034-X. doi:, 10.1016/j.str.2016.03.023. PMID:27133025 doi:https://dx.doi.org/10.1016/j.str.2016.03.023

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OCA

[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] Ferrao R, Wallweber HJ, Ho H, Tam C, Franke Y, Quinn J, Lupardus PJ. The Structural Basis for Class II Cytokine Receptor Recognition by JAK1. Structure. 2016 Apr 27. pii: S0969-2126(16)30034-X. doi:, 10.1016/j.str.2016.03.023. PMID:27133025 doi:https://dx.doi.org/10.1016/j.str.2016.03.023

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5ixi | pdb_00005ixi

Structure of human JAK1 FERM/SH2 in complex with IFNLR1/IL10RA chimera

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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