Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant

Metcalfe R Hanssen E, Fung K, Aizel K, Kosasih C, Zlatic C, Doughty L, Morton C, Leis A, Parker M, Gooley P, Putoczki T, Griffin M, Nature Communications 14(1) (2023) DOI

SASDLM3 – Interleukin-11 signalling complex, truncated gp130

Interleukin-6 receptor subunit beta
Interleukin-11
Interleukin-11 receptor subunit alpha
MWexperimental 182 kDa
MWexpected 170 kDa
VPorod 405 nm3
log I(s) 6.75×10-2 6.75×10-3 6.75×10-4 6.75×10-5
Interleukin-6 receptor subunit beta Interleukin-11 Interleukin-11 receptor subunit alpha small angle scattering data  s, nm-1
ln I(s)
Interleukin-6 receptor subunit beta Interleukin-11 Interleukin-11 receptor subunit alpha Guinier plot ln 6.76×10-2 Rg: 5.3 nm 0 (5.3 nm)-2 s2
(sRg)2I(s)/I(0)
Interleukin-6 receptor subunit beta Interleukin-11 Interleukin-11 receptor subunit alpha Kratky plot 1.104 0 3 sRg
p(r)
Interleukin-6 receptor subunit beta Interleukin-11 Interleukin-11 receptor subunit alpha pair distance distribution function Rg: 5.4 nm 0 Dmax: 17.6 nm

Data validation


Fits and models


log I(s)
 s, nm-1
Interleukin-6 receptor subunit beta Interleukin-11 Interleukin-11 receptor subunit alpha OTHER model

log I(s)
 s, nm-1
Interleukin-6 receptor subunit beta Interleukin-11 Interleukin-11 receptor subunit alpha DAMMIN model

Synchrotron SAXS data from solutions of Interleukin-11 signalling complex, truncated gp130 in 20 mM Tris, 150 mM NaCl, 0.2% sodium azide, pH 8.5 were collected on the SAXS/WAXS beam line at the Australian Synchrotron storage ring (Melbourne, Australia) using a Pilatus3 S 2M detector at a sample-detector distance of 3.5 m and at a wavelength of λ = 0.108 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). In-line size-exclusion chromatography (SEC) SAS was employed. The SEC parameters were as follows: A sample at 2 mg/ml was injected at a 0.45 ml/min flow rate onto a GE Superdex 200 Increase 10/300 column at 20°C. 12 successive 1 second frames were collected. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted.

Sample injection volume = UNKNOWN

Interleukin-6 receptor subunit beta (gp130 D1-D3)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   34.5 kDa
 
UniProt   P40189 (22-324)
Sequence   FASTA
 
Interleukin-11
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   18.2 kDa
 
UniProt   P20809 (32-199)
Sequence   FASTA
 
Interleukin-11 receptor subunit alpha
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   32.2 kDa
 
UniProt   Q14626 (23-319)
Sequence   FASTA
 
PDB ID   8DPT