Clustering of aromatic residues in prion-like domains can tune the formation, state, and organization of biomolecular condensates

Full item page Simple item page

• dc.contributor.author Holehouse, Alex S.
• dc.contributor.author Ginell, Garret M.
• dc.contributor.author Griffith, Daniel
• dc.contributor.author Böke, Elvan
• dc.date.accessioned 2022-03-08T10:27:13Z
• dc.date.available 2022-03-08T10:27:13Z
• dc.date.issued 2021
• dc.description.abstract In immature oocytes, Balbiani bodies are conserved membraneless condensates implicated in oocyte polarization, the organization of mitochondria, and long-term organelle and RNA storage. In Xenopus laevis, Balbiani body assembly is mediated by the protein Velo1. Velo1 contains an N-terminal prion-like domain (PLD) that is essential for Balbiani body formation. PLDs have emerged as a class of intrinsically disordered regions that can undergo various different types of intracellular phase transitions and are often associated with dynamic, liquid-like condensates. Intriguingly, the Velo1 PLD forms solid-like assemblies. Here we sought to understand why Velo1 phase behavior appears to be biophysically distinct from that of other PLD-containing proteins. Through bioinformatic analysis and coarse-grained simulations, we predict that the clustering of aromatic residues and the amino acid composition of residues between aromatics can influence condensate material properties, organization, and the driving forces for assembly. To test our predictions, we redesigned the Velo1 PLD to test the impact of targeted sequence changes in vivo. We found that the Velo1 design with evenly spaced aromatic residues shows rapid internal dynamics, as probed by fluorescent recovery after photobleaching, even when recruited into Balbiani bodies. Our results suggest that Velo1 might have been selected in evolution for distinctly clustered aromatic residues to maintain the structure of Balbiani bodies in long-lived oocytes. In general, our work identifies several tunable parameters that can be used to augment the condensate material state, offering a road map for the design of synthetic condensates.
• dc.description.sponsorship Funding for this project was provided by the National Science Foundation Grant DGE-2139839 (to D.G.), and an ERC Starting Grant (ERC-StG-2017 759107) and MINECO’s Proyectos de Excelencia (BFU2017-89373-P) (both to E.B.). E.B. also acknowledges support from the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya
• dc.format.mimetype application/pdf
• dc.identifier.citation Holehouse AS, Ginell GM, Griffith D, Böke E. Clustering of aromatic residues in prion-like domains can tune the formation, state, and organization of biomolecular condensates. Biochemistry. 2021 Nov 30;60(47):3566-3581. DOI: 10.1021/acs.biochem.1c00465
• dc.identifier.doi http://dx.doi.org/10.1021/acs.biochem.1c00465
• dc.identifier.issn 1520-4995
• dc.identifier.uri http://hdl.handle.net/10230/52646
• dc.language.iso eng
• dc.publisher American Chemical Society (ACS)
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/759107
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/ BFU2017-89373-P
• dc.rights © 2021 Alex S. Holehuse, Garrett M. Ginell, Daniel Griffith, Elvan Bröke. Published by American Chemical Society. Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/)
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.other Biologia molecular
• dc.subject.other Cèl·lules
• dc.subject.other Proteïnes
• dc.title Clustering of aromatic residues in prion-like domains can tune the formation, state, and organization of biomolecular condensates
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion