Conformational Dynamics of the Soluble and Membrane-Bound Forms of Interleukin-1 Receptor Type-1: Insights into Linker Flexibility and Domain Orientation
Abstract
:1. Introduction
2. Results
2.1. Conformational Dynamics of Soluble and Membrane-Bound IL-1R1-ECDs
2.2. Principal Component Analysis of Soluble and Membrane-Bound IL-1R1-ECDs MD Trajectories
2.3. Clustering Analysis of Soluble and Membrane-Bound IL-1R1-ECDs Conformations
3. Discussion
4. Materials and Methods
4.1. Protein Structure of Soluble IL-1R1 (ECD)
4.2. Structural Assembly and Refinement of a Full-Length IL-1R1
4.3. Construction of the Full-Length IL-1R1 Membrane System
4.4. MD Simulations of Full-Length IL-1R1 Membrane System
4.5. MD Simulations of Soluble IL-1R1 (ECD)
4.6. Principal Component Analysis
4.7. Clustering Based on the Backbone Dihedral Angles of the Flexible Linker
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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System | Average RMSD (Å) | Rg (nm) | # HBintra | SASA (nm2) |
---|---|---|---|---|
4GAF 1 | -- | 3.0 | 229 | 179.4 |
1G0Y | 16.8 | 2.2 | 249 | 174.4 |
S1 | 18.8 ± 0.22 | 2.9 ± 0.17 | 234 ± 7 | 178.7 ± 4.25 |
S2 | 16.5 ± 0.02 | 2.2 ± 0.06 | 240 ± 8 | 173.0 ± 2.74 |
S3 | 16.9 ± 0.04 | 2.2 ± 0.04 | 241 ± 7 | 172.7 ± 3.13 |
S4 | 20.6 ± 0.24 | 2.8 ± 0.20 | 233 ± 7 | 178.9 ± 3.77 |
S5 | 15.6 ± 0.20 | 2.4 ± 0.19 | 234 ± 8 | 176.4 ± 4.50 |
M1 | 14.1 ± 0.07 | 2.3 ± 0.18 | 239 ± 7 | 175.8 ± 4.28 |
M2 | 17.3 ± 0.13 | 3.1 ± 0.08 | 231 ± 7 | 184.7 ± 2.88 |
M3 | 11.7 ± 0.11 | 3.3 ± 0.15 | 232 ± 7 | 186.3 ± 2.60 |
M4 | 15.6 ±0.18 | 3.0 ± 0.15 | 233 ± 8 | 183.2 ± 3.13 |
M5 | 14.1 ±0.06 | 2.3 ± 0.18 | 238 ± 7 | 175.3 ± 4.35 |
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Luís, J.P.; Mata, A.I.; Simões, C.J.V.; Brito, R.M.M. Conformational Dynamics of the Soluble and Membrane-Bound Forms of Interleukin-1 Receptor Type-1: Insights into Linker Flexibility and Domain Orientation. Int. J. Mol. Sci. 2022, 23, 2599. https://doi.org/10.3390/ijms23052599
Luís JP, Mata AI, Simões CJV, Brito RMM. Conformational Dynamics of the Soluble and Membrane-Bound Forms of Interleukin-1 Receptor Type-1: Insights into Linker Flexibility and Domain Orientation. International Journal of Molecular Sciences. 2022; 23(5):2599. https://doi.org/10.3390/ijms23052599
Chicago/Turabian StyleLuís, João P., Ana I. Mata, Carlos J. V. Simões, and Rui M. M. Brito. 2022. "Conformational Dynamics of the Soluble and Membrane-Bound Forms of Interleukin-1 Receptor Type-1: Insights into Linker Flexibility and Domain Orientation" International Journal of Molecular Sciences 23, no. 5: 2599. https://doi.org/10.3390/ijms23052599