Disordered regions of DBHS proteins play distinct roles in protein condensation behaviour

Research output: Contribution to conferencePoster


The huge diversity of stable folded structures formed by proteins with complex amino acid sequences has been well characterised and can be confidently predicted in most cases. A large proportion of proteins, however, contain regions enriched in only a few amino acids – low complexity regions (LCRs) – commonly predicted to be intrinsically disordered. Relationships between the amino acid composition of LCRs, protein structure, material behaviour and function are poorly understood. DBHS proteins are RNA- and DNA-binding proteins that are particularly abundant in the mammalian cell nucleus, involved in transcription, RNA-processing and formation of membraneless organelles. While DBHS proteins have a highly conserved core folded dimerisation domain, their extended LCRs at each terminus are highly diverse, providing a unique opportunity for determining composition-function relationships of LCRs. We have shown that the LCRs of these proteins are central to their ability to functionally condense via a process called liquid-liquid phase separation, driving the dynamic, reversible de-mixing of molecules in the nucleus. Using various in vitro biophysical assays combined with protein localisation studies in cell culture, we aim to understand how amino acid composition of these LCRs determines protein material state and function. Importantly, our work indicates that the condensation behaviour conferred by a given LCR on a protein is context-dependent, that is, dependent on the composition of other regions present in the protein. Unexpectedly, we have found that the longest LCR found in DBHS proteins, which also has a prion-like composition, actually attenuates the condensation propensity of the protein. Our data add nuance to the emerging paradigm that intrinsically disordered LCRs drive condensation of proteins in the cell.
Original languageEnglish
Publication statusPublished - 2023
Event48th Lorne Conference on Protein Structure & Function - Mantra Lorne, Lorne, Australia
Duration: 5 Feb 20239 Feb 2023


Conference48th Lorne Conference on Protein Structure & Function
Abbreviated titleLorne Proteins 2023
Internet address


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