Balasubramanian, S and Maharana, S and Srivastava, A (2023) �Boundary residues� between the folded RNA recognition motif and disordered RGG domains are critical for FUS�RNA binding. In: Journal of Biological Chemistry, 299 (12).
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Abstract
Fused in sarcoma (FUS) is an abundant RNA-binding protein, which drives phase separation of cellular condensates and plays multiple roles in RNA regulation. The RNA-binding ability of FUS protein is crucial to its cellular function. Here, our molecular simulation study on the FUS�RNA complex provides atomic resolution insights into the observations from biochemical studies and also illuminates our understanding of molecular driving forces that mediate the structure, stability, and interaction of the RNA recognition motif (RRM) and RGG domains of FUS with a stem�loop junction RNA. We observe clear cooperativity and division of labor among the ordered (RRM) and disordered domains (RGG1 and RGG2) of FUS that leads to an organized and tighter RNA binding. Irrespective of the length of RGG2, the RGG2�RNA interaction is confined to the stem�loop junction and the proximal stem regions. On the other hand, the RGG1 interactions are primarily with the longer RNA stem. We find that the C terminus of RRM, which make up the �boundary residues� that connect the folded RRM with the long disordered RGG2 stretch of the protein, plays a critical role in FUS�RNA binding. Our study provides high-resolution molecular insights into the FUS�RNA interactions and forms the basis for understanding the molecular origins of full-length FUS interaction with RNA. © 2023 The Authors
| Item Type: | Journal Article |
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| Publication: | Journal of Biological Chemistry |
| Publisher: | American Society for Biochemistry and Molecular Biology Inc. |
| Additional Information: | The copyright for this article belongs to Author. |
| Keywords: | Molecular structure; Phase separation; Proteins; Tumors, Fused in sarcomata; Low-complexity domain; Lower complexity; Molecular simulations; RNA binding; RNA interaction; RNA-recognition motifs; RNA�fused in sarcoma binding; Stem-loop, RNA |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 29 Feb 2024 05:58 |
| Last Modified: | 29 Feb 2024 05:58 |
| URI: | https://eprints.iisc.ac.in/id/eprint/83733 |
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