5l04

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^[1]

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