5L04

STRUCTURE OF INTERFERON LAMBDA 1 RECEPTOR WITH HUMAN KINASE JAK1

Summary for 5L04

• Entry DOI: 10.2210/pdb5l04/pdb
• Descriptor: Tyrosine-protein kinase JAK1, Interferon lambda receptor 1 (3 entities in total)
• Functional Keywords: complex of jak1 and interferon lambda 1, jak kinase, intracellular domain of ifnlr1, ferm domain, sh2-like domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 69430.31

Authors

Lubkowski, J.,Wlodawer, A.,Zhang, D. (deposition date: 2016-07-26, release date: 2016-10-12, Last modification date: 2024-03-06)

Primary citation

Zhang, D.,Wlodawer, A.,Lubkowski, J.
Crystal Structure of a Complex of the Intracellular Domain of Interferon lambda Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.
J. Mol. Biol., 428:4651-4668, 2016

PubMed 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.

PubMed: 27725180
DOI: 10.1016/j.jmb.2016.10.005

Experimental method

X-RAY DIFFRACTION (2.1 Å)