PDBsum entry 5ixd

Cytokine

PDB id: 5ixd

Contents

Protein chains

420 a.a.

21 a.a.

Ligands

CIT

PDB id:

5ixd

Name:

Cytokine

Title:

Structure of human jak1 ferm/sh2 in complex with ifn lambda receptor

Structure:

Tyrosine-protein kinase jak1. Chain: a. Fragment: unp residues 35-559. Synonym: janus kinase 1,jak-1. Engineered: yes. Interferon lambda receptor 1. Chain: b. Fragment: unp residues 250-299. Synonym: ifn-lambda-r1,cytokine receptor class-ii member 12,cytokine

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: jak1, jak1a, jak1b. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Gene: ifnlr1, il28ra, licr2.

Resolution:

2.85Å R-factor: 0.252 R-free: 0.282

Authors:

R.Ferrao,H.J.A.Wallweber,P.J.Lupardus

Key ref:

R.Ferrao et al. (2016). The Structural Basis for Class II Cytokine Receptor Recognition by JAK1. Structure, 24, 897-905. PubMed id: 27133025 DOI: 10.1016/j.str.2016.03.023

Date:

23-Mar-16 Release date: 18-May-16

Protein chain

P23458  (JAK1_HUMAN) -  Tyrosine-protein kinase JAK1 from Homo sapiens

Seq: 1154 a.a.

Struc: 420 a.a.*

Protein chain

Q8IU57  (INLR1_HUMAN) -  Interferon lambda receptor 1 from Homo sapiens

Seq: 520 a.a.

Struc: 21 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chain A: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.str.2016.03.023

Structure 24:897-905 (2016)

PubMed id: 27133025

The Structural Basis for Class II Cytokine Receptor Recognition by JAK1.

R.Ferrao, H.J.Wallweber, H.Ho, C.Tam, Y.Franke, J.Quinn, P.J.Lupardus.

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.