Visualization of liquid-liquid phase transitions using a tiny G-quadruplex binding protein
Liquid-liquid phase transitions govern a wide range of protein-protein and protein-RNA interactions. Although the importance of multivalency and protein disorder in driving these transitions is clear, there is limited knowledge concerning the structural basis of phase transitions or the conformational changes that accompany this process. In this work, we found that a small human protein, SERF2, is important for the formation of stress granules. We determined the solution NMR structure ensemble of SERF2. We show that SERF2 specifically interacts with non-canonical tetrahelical RNA structures called G-quadruplexes, structures linked to stress granule formation. The biophysical amenability of both SERF2 and RNA G4 quadruplexes have allowed us to characterize the multivalent protein-RNA interactions involved in liquid-liquid phase transitions, the role that protein disorder plays in these transitions, identify the specific contacts involved, and describe how these interactions impact the structural dynamics of the components enabling a detailed understanding of the structural transitions involved in early stages of ribonucleoprotein condensate formation.
Authors
- Emi Miyashita
- Bryan B. Guzmán (ORCID: https://orcid.org/0000-0002-2711-9533)
- James C.A. Bardwell (ORCID: https://orcid.org/0000-0003-1683-1944)
- Alexander Kovalenko (ORCID: https://orcid.org/0000-0003-3131-6107)
- Bikash R. Sahoo (ORCID: https://orcid.org/0000-0002-3683-1178)
- Harry Yang (ORCID: https://orcid.org/0009-0008-8758-5705)
- Nathan Clark
- Vojč Kocman (ORCID: https://orcid.org/0000-0002-5644-7245)
- Sarah E. Harris (ORCID: https://orcid.org/0000-0002-4807-2578)
- J. Damon Hoff (ORCID: https://orcid.org/0000-0002-4054-848X)
- Ee Lin Wong
- Xiexiong Deng (ORCID: https://orcid.org/0000-0002-0025-5383)
- Subramanian Vivekanandan (ORCID: https://orcid.org/0000-0003-4338-6153)
- Janez Plavec (ORCID: https://orcid.org/0000-0003-1570-8602)
- Daniel Dominguez (ORCID: https://orcid.org/0000-0002-8630-2776)
- Hirohide Saito (ORCID: https://orcid.org/0000-0002-8570-5784)
- Budheswar Dehury (ORCID: https://orcid.org/0000-0002-9726-8454)
Institutions
- University of North Carolina at Chapel Hill (US)
- Howard Hughes Medical Institute (US)
- University of Kentucky (US)
- Manipal Academy of Higher Education (IN)
- Kyoto University (JP)
- University of Michigan (US)
- Michigan Medicine (US)
- National Institute of Chemistry (SI)
- The University of Tokyo (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1038/s41467-025-63597-7
- Citations
- 1
- Primary Topic
- DNA and Nucleic Acid Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.81