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 Nov 20)

doi: 10.1038/s41467-023-42754-w
Submitted to SASBDB: 2021 Apr 12
Published in SASBDB:

SASDLM3 – Interleukin-11 signalling complex, truncated gp130

Interleukin-6 receptor subunit betaInterleukin-11Interleukin-11 receptor subunit alpha experimental SAS data
OTHER model
Sample: Interleukin-6 receptor subunit beta dimer, 69 kDa Homo sapiens protein
Interleukin-11 dimer, 36 kDa Homo sapiens protein
Interleukin-11 receptor subunit alpha dimer, 64 kDa Homo sapiens protein
Buffer: 20 mM Tris, 150 mM NaCl, 0.2% sodium azide, pH: 8.5
Experiment: SAXS data collected at SAXS/WAXS, Australian Synchrotron on 2019 Jun 8
RgGuinier 5.3 nm
Dmax 17.6 nm
VolumePorod 405 nm3

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

Interleukin-11Interleukin-11 receptor subunit alphaInterleukin-6 receptor subunit beta experimental SAS data
OTHER model
Sample: Interleukin-11 dimer, 36 kDa Homo sapiens protein
Interleukin-11 receptor subunit alpha dimer, 64 kDa Homo sapiens protein
Interleukin-6 receptor subunit beta dimer, 134 kDa Homo sapiens protein
Buffer: 20 mM Tris, 150 mM NaCl, 0.2% sodium azide, pH: 8.5
Experiment: SAXS data collected at SAXS/WAXS, Australian Synchrotron on 2019 Nov 28
RgGuinier 6.2 nm
Dmax 20.7 nm
VolumePorod 710 nm3

SASDLP3 – Interleukin 11 complex with IL-11Rα and gp130 D2-D3

Interleukin-11 receptor subunit alphaInterleukin 11Interleukin-6 receptor subunit beta experimental SAS data
OTHER model
Sample: Interleukin-11 receptor subunit alpha monomer, 32 kDa Homo sapiens protein
Interleukin 11 monomer, 18 kDa Homo sapiens protein
Interleukin-6 receptor subunit beta monomer, 23 kDa Homo sapiens protein
Buffer: 20 mM Tris, 150 mM NaCl, 0.2% sodium azide, pH: 8.5
Experiment: SAXS data collected at SAXS/WAXS, Australian Synchrotron on 2019 Jun 8
RgGuinier 3.6 nm
Dmax 12.9 nm
VolumePorod 127 nm3

SASDLS3 – Interleukin 11 Mutein, complex with gp130 (domains 1-3) and IL-11Rα

Interleukin-11 receptor subunit alphaInterleukin 11 MuteinInterleukin-6 receptor subunit beta experimental SAS data
DAMMIN model
Sample: Interleukin-11 receptor subunit alpha monomer, 32 kDa Homo sapiens protein
Interleukin 11 Mutein monomer, 18 kDa Homo sapiens protein
Interleukin-6 receptor subunit beta monomer, 35 kDa Homo sapiens protein
Buffer: 20 mM Tris, 150 mM NaCl, 0.2% sodium azide, pH: 8.5
Experiment: SAXS data collected at SAXS/WAXS, Australian Synchrotron on 2019 Jun 8
RgGuinier 4.4 nm
Dmax 15.6 nm
VolumePorod 160 nm3

SASDLR3 – Interleukin 11 Mutein

Interleukin 11 Mutein experimental SAS data
OTHER model
Sample: Interleukin 11 Mutein monomer, 18 kDa Homo sapiens protein
Buffer: 20 mM Tris, 150 mM NaCl, 0.2% sodium azide, pH: 8.5
Experiment: SAXS data collected at SAXS/WAXS, Australian Synchrotron on 2019 Jun 8
RgGuinier 1.8 nm
Dmax 5.4 nm
VolumePorod 25 nm3

SASDLQ3 – Interleukin 11, W168A mutant

Interleukin-11 (W168A) experimental SAS data
OTHER model
Sample: Interleukin-11 (W168A) monomer, 18 kDa Homo sapiens protein
Buffer: 20 mM Tris, 150 mM NaCl, 0.2% sodium azide, pH: 8.5
Experiment: SAXS data collected at SAXS/WAXS, Australian Synchrotron on 2019 Nov 28
RgGuinier 1.7 nm
Dmax 5.2 nm
VolumePorod 22 nm3