5IXD

Structure of human JAK1 FERM/SH2 in complex with IFN lambda receptor

Summary for 5IXD

• Entry DOI: 10.2210/pdb5ixd/pdb
• Related: 5IXI
• Descriptor: Tyrosine-protein kinase JAK1, Interferon lambda receptor 1, CITRIC ACID (3 entities in total)
• Functional Keywords: jak kinase, jak1, ifnlr1, interferon, cytokine
• Biological source: Homo sapiens (Human); More
• Cellular location: Endomembrane system; Peripheral membrane protein: P23458; Membrane ; Single-pass type I membrane protein : Q8IU57
• Total number of polymer chains: 2
• Total formula weight: 69691.33

Authors

Ferrao, R.,Wallweber, H.J.A.,Lupardus, P.J. (deposition date: 2016-03-23, release date: 2016-05-18, Last modification date: 2023-09-27)

Primary citation

Ferrao, R.,Wallweber, H.J.,Ho, H.,Tam, C.,Franke, Y.,Quinn, J.,Lupardus, P.J.
The Structural Basis for Class II Cytokine Receptor Recognition by JAK1.
Structure, 24:897-905, 2016

PubMed Abstract: 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-λ 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.

PubMed: 27133025
DOI: 10.1016/j.str.2016.03.023

Experimental method

X-RAY DIFFRACTION (2.85 Å)