5l04: Difference between revisions
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/JAK1_HUMAN 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. [[http://www.uniprot.org/uniprot/INLR1_HUMAN 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.<ref>PMID:12521379</ref> <ref>PMID:12469119</ref> <ref>PMID:12483210</ref> | [[http://www.uniprot.org/uniprot/JAK1_HUMAN 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. [[http://www.uniprot.org/uniprot/INLR1_HUMAN 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.<ref>PMID:12521379</ref> <ref>PMID:12469119</ref> <ref>PMID:12483210</ref> | ||
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== Publication Abstract from PubMed == | |||
The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-lambda receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1A. In this structure, the receptor peptide forms an 85-A-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-alpha receptor and TYK2. | |||
Crystal Structure of a Complex of the Intracellular Domain of Interferon lambda Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.,Zhang D, Wlodawer A, Lubkowski J J Mol Biol. 2016 Nov 20;428(23):4651-4668. doi: 10.1016/j.jmb.2016.10.005. Epub, 2016 Oct 7. PMID:27725180<ref>PMID:27725180</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 07:54, 12 April 2017
STRUCTURE OF INTERFERON LAMBDA 1 RECEPTOR WITH HUMAN KINASE JAK1STRUCTURE OF INTERFERON LAMBDA 1 RECEPTOR WITH HUMAN KINASE JAK1
Structural highlights
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 PubMedThe crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-lambda receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1A. In this structure, the receptor peptide forms an 85-A-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-alpha receptor and TYK2. Crystal Structure of a Complex of the Intracellular Domain of Interferon lambda Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.,Zhang D, Wlodawer A, Lubkowski J J Mol Biol. 2016 Nov 20;428(23):4651-4668. doi: 10.1016/j.jmb.2016.10.005. Epub, 2016 Oct 7. PMID:27725180[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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