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

SASDLN3 – Interleukin 11 signalling complex, full-length extracellular gp130

Interleukin-11
Interleukin-11 receptor subunit alpha
Interleukin-6 receptor subunit beta
MWexperimental 291 kDa
MWexpected 235 kDa
VPorod 710 nm3
log I(s) 3.86×10-2 3.86×10-3 3.86×10-4 3.86×10-5
Interleukin-11 Interleukin-11 receptor subunit alpha Interleukin-6 receptor subunit beta small angle scattering data  s, nm-1
ln I(s)
Interleukin-11 Interleukin-11 receptor subunit alpha Interleukin-6 receptor subunit beta Guinier plot ln 3.87×10-2 Rg: 6.2 nm 0 (6.2 nm)-2 s2
(sRg)2I(s)/I(0)
Interleukin-11 Interleukin-11 receptor subunit alpha Interleukin-6 receptor subunit beta Kratky plot 1.104 0 3 sRg
p(r)
Interleukin-11 Interleukin-11 receptor subunit alpha Interleukin-6 receptor subunit beta pair distance distribution function Rg: 6.3 nm 0 Dmax: 20.7 nm

Data validation


Fits and models


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

Synchrotron SAXS data from solutions of Interleukin 11 signalling complex, full-length extracellular 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 2.2 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 0.40 ml/min flow rate onto a GE Superdex 200 Increase 10/300 column at 20°C. Eight 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-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
 
Interleukin-6 receptor subunit beta
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   67.1 kDa
 
UniProt   P40189 (23-612)
Sequence   FASTA
 
PDB ID   8DPT