Accurate model of liquid–liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties
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- Giulio Tesei
- Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark;
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- Thea K. Schulze
- Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark;
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- Ramon Crehuet
- Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark;
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- Kresten Lindorff-Larsen
- Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark;
抄録
<jats:title>Significance</jats:title> <jats:p>Cells may compartmentalize proteins via a demixing process known as liquid–liquid phase separation (LLPS), which is often driven by intrinsically disordered proteins (IDPs) and regions. Protein condensates arising from LLPS may develop into insoluble protein aggregates, as in neurodegenerative diseases and cancer. Understanding the process of formation, dissolution, and aging of protein condensates requires models that accurately capture the underpinning interactions at the residue level. In this work, we leverage data from biophysical experiments on IDPs in dilute solution to develop a sequence-dependent model which predicts conformational and phase behavior of diverse and unrelated protein sequences with good accuracy. Using the model, we gain insight into the coupling between chain compaction and LLPS propensity.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 118 (44), 2021-10-29
Proceedings of the National Academy of Sciences