title: Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.
abstract: 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-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-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-α receptor and TYK2.
authors.affiliation: Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: wlodawer@nih.gov.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wlodawer
authors.affiliation: Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: lubkowsj@mail.nih.gov.
authors.forename: Jacek
authors.initials: J
authors.lastname: Lubkowski
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D053613:Janus Kinase 1 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000378:metabolism*; D017471:Receptors, Interferon
chemical_list: C579640:IFNLR1 protein, human; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; C507904:JAK1 protein, human; D053613:Janus Kinase 1
keywords: JAK/STAT signaling; Janus kinases; cytokine receptors; protein–protein interactions; structure comparisons