RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation
SCIE
SCOPUS
- Title
- RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation
- Authors
- Guillen-Boixet, Jordina; Kopach, Andrii; Holehouse, Alex S.; Wittmann, Sina; Jahnel, Marcus; Schluessler, Raimund; Kim, Kyoohyun; Trussina, Irmela R. E. A.; Wang, Jie; Mateju, Daniel; Poser, Ina; Maharana, Shovamayee; Ruer-Gruss, Martine; Richter, Doris; Zhang, Xiaojie; Chang, Young-Tae; Guck, Jochen; Honigmann, Alf; Mahamid, Julia; Hyman, Anthony A.; Pappu, Rohit V.; Alberti, Simon; Franzmann, Titus M.
- Date Issued
- 2020-04
- Publisher
- CELL PRESS
- Abstract
- Stressed cells shut down translation, release mRNA molecules from polysomes, and form stress granules (SGs) via a network of interactions that involve G3BP. Here we focus on the mechanistic underpinnings of SG assembly. We show that, under non-stress conditions, G3BPadopts a compact auto-inhibited state stabilized by electrostatic intramolecular interactions between the intrinsically disordered acidic tracts and the positively charged arginine-rich region. Upon release from polysomes, unfolded mRNAs outcompete G3BP auto-inhibitory interactions, engendering a conformational transition that facilitates clustering of G3BP through protein-RNA interactions. Subsequent physical crosslinking of G3BP clusters drives RNA molecules into networked RNA/protein condensates. We show that G3BP condensates impede RNA entanglement and recruit additional client proteins that promote SG maturation or induce a liquid-to-solid transition that may underlie disease. We propose that condensation coupled to conformational rearrangements and hetero-typic multivalent interactions may be a general principle underlying RNP granule assembly.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/103886
- DOI
- 10.1016/j.cell.2020.03.049
- ISSN
- 0092-8674
- Article Type
- Article
- Citation
- CELL, vol. 181, no. 2, page. 346 - +, 2020-04
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- There are no files associated with this item.
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