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Computer-based design of sensors that can monitor endogenous Ras activity

January 25, 2024
in Science
Computer-based design of sensors that can monitor endogenous Ras activity
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Many questions on the activity of the Ras proto-oncogene are unanswered due to the lack of tools for detecting active Ras in living cells. Here, we used protein design and structure prediction algorithms to develop biosensors that detect the activity and environment of endogenous Ras.

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Fig. 1: Design of Ras sensors.

References

Chiu, V. K. et al. Ras signalling on the endoplasmic reticulum and the Golgi. Nat. Cell Biol. 4, 343–350 (2002). This paper describes one of the first tools for measuring Ras activity.

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Mochizuki, N. et al. Spatiotemporal images of growth-factor-induced activation of Ras and Rap1. Nature 411, 1065–1068 (2001). This paper describes one of the first sensors for Ras activity.

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Langan, R. A. et al. De novo design of bioactive protein switches. Nature 572, 205–210 (2019). This paper presents LOCKR, the first de novo protein switch system.

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Zhang, J. Z. et al. Thermodynamically coupled biosensors for detecting neutralizing antibodies against SARS-CoV-2 variants. Nat Biotechnol. https://doi.org/10.1038/s41587-022-01280-8 (2022). This paper shows LOCKR as a useful biosensor for a clinically relevant target.

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Tulpule, A. et al. Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules. Cell 184, 2649–2664.e18 (2021). This work shows that a fusion oncoprotein (EML4-ALK) forms cytosolic granules to activate Ras signaling.

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Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Zhang, J. Z. et al. Computationally designed sensors detect endogenous Ras activity and signaling effectors at subcellular resolution. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-02107-w (2024).

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Computer-based design of sensors that can monitor endogenous Ras activity.
Nat Biotechnol (2024). https://doi.org/10.1038/s41587-023-02108-9

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Published: 25 January 2024

DOI: https://doi.org/10.1038/s41587-023-02108-9

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