PDBsum entry 5uwc

Signaling protein

PDB id: 5uwc

Contents

Protein chains

253 a.a.

112 a.a.

Ligands

NAG-NAG-FUL

NAG

CIT ×2

IMD

EDT

Waters ×64

PDB id:

5uwc

Name:

Signaling protein

Title:

Cytokine-receptor complex

Structure:

Interleukin-3 receptor subunit alpha. Chain: g. Fragment: unp residues 20-307. Synonym: il-3ra. Engineered: yes. Mutation: yes. Interleukin-3. Chain: i. Fragment: unp residues 31-152.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: il3ra, il3r. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: il3. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.40Å R-factor: 0.218 R-free: 0.242

Authors:

S.E.Broughton,M.W.Parker

Key ref:

S.E.Broughton et al. (2018). A dual role for the N-terminal domain of the IL-3 receptor in cell signalling. Nat Commun, 9, 386. PubMed id: 29374162

Date:

21-Feb-17 Release date: 07-Feb-18

Protein chain

P26951  (IL3RA_HUMAN) -  Interleukin-3 receptor subunit alpha from Homo sapiens

Seq: 378 a.a.

Struc: 253 a.a.*

Protein chain

P08700  (IL3_HUMAN) -  Interleukin-3 from Homo sapiens

Seq: 152 a.a.

Struc: 112 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Nat Commun 9:386 (2018)

PubMed id: 29374162

A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.

S.E.Broughton, T.R.Hercus, T.L.Nero, W.L.Kan, E.F.Barry, M.Dottore, K.S.Cheung Tung Shing, C.J.Morton, U.Dhagat, M.P.Hardy, N.J.Wilson, M.T.Downton, C.Schieber, T.P.Hughes, A.F.Lopez, M.W.Parker.

ABSTRACT

The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function.