5IXI

Structure of human JAK1 FERM/SH2 in complex with IFNLR1/IL10RA chimera

5IXI の概要

• エントリーDOI: 10.2210/pdb5ixi/pdb
• 関連するPDBエントリー: 5IXD
• 分子名称: Tyrosine-protein kinase JAK1, Chimera protein of Interferon lambda receptor 1 and Interleukin-10 receptor subunit alpha (3 entities in total)
• 機能のキーワード: jak kinase, jak1, ifnlr1, il10, il10ra, interferon, cytokine
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Endomembrane system; Peripheral membrane protein: P23458; Membrane; Single-pass type I membrane protein: Q13651
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69498.40

構造登録者

Ferrao, R.,Wallweber, H.J.A.,Lupardus, P.J. (登録日: 2016-03-23, 公開日: 2016-05-18, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.57 Å)