Trends in Biochemical Sciences
ReviewMaking the Case for Disordered Proteins and Biomolecular Condensates in Bacteria
Section snippets
Biochemical Reactions Have to Be Organized in Space and Time
Spatial and temporal regulation of cellular matter is necessary for the control of transcription, protein quality control, cell signaling, and responses to stimuli [1]. In many eukaryotic systems as well as in bacterial systems (the focus of this article), the reversible formation of membraneless biomolecular condensates – referred to hereafter as condensates – provides the necessary spatiotemporal control by organizing biochemical reactions, enabling quality control, and concentrating cellular
Principles Underlying Phase Transitions of Multivalent Macromolecules
Interchain physical crosslinks among stickers enables a networking transition known as bond percolation [10,13., 14., 15.,17,18]. This happens above a system-specific threshold concentration known as the percolation threshold that is designated as cperc. Above cperc, the collection of multivalent macromolecules in solution will form a system-spanning network [11,14,15] (Figure 2). These transitions are also known as sol–gel transitions [26], but we prefer the term bond percolation to avoid
Spatiotemporal Control of Bacterial Division
The initiation of cell division in rod-shaped bacteria is marked by the formation of a cytokinetic ring at the cell center [70]. A family of proteins, termed the divisome, collectively functions to constrict the ring in the center of the cell, synthesize new material, and pinch the cell in two [71]. The bacterial cytokinetic ring is scaffolded by the tubulin homolog FtsZ that serves as a treadmilling interaction hub for many of the adaptor proteins of the divisome [72., 73., 74.]. FtsZ
Spatiotemporal Control of Polarity
Another area of spatial and temporal organization pertains to the regulation of asymmetric division and polarity that has been reported in Caulobacter crescentus. Here, a differentiated stalked cell can enter the cell division cycle and in doing so, it ensures that the cytoplasmic space has two sides: a future swarmer and the old stalk cell [69,92,93]. Polar organizing protein (Pop)Z is 57% disordered and it is a major player in differentiation [92,94,95]. PopZ oligomerizes and forms an
Control of DNA Replication
In bacterial DNA replication and repair, single-stranded DNA binding proteins (SSBs) play an essential role. Their modular architecture, which is reminiscent of FtsZ, includes an ordered DNA-binding domain (OB fold), followed by a hypervariable intrinsically disordered linker (IDL/spacer) that is connected to a conserved C-terminal tip (sticker) [63,64,102]. SSBs oligomerize to form homotetramers that leads to a fourfold increase in the valence of stickers that coordinate interactions with SSB
Control of Transcription
Transcriptional foci in E. coli also involve RNAP and bear the hallmarks of condensates. In slow-growing conditions, RNAP is uniformly dispersed throughout the cell, whereas in fast-growing conditions, RNAP becomes localized to distinct puncta, potentially optimizing ribosomal production [108., 109., 110.] – akin to nucleoli in eukaryotes [38]. Puncta that were previously thought to form via DNA binding were shown to dissolve with the addition of 1′6 hexanediol to the media, indicating that the
Bacterial Condensates in Protein Quality Control
Another process controlled by condensates in bacteria is that of RNA degradation [112., 113., 114.]. In this system, RNaseE is a critical driver of the formation of the RNA degradasome. The architecture of RNaseE includes a conserved DEAD-box RNA helicase and a disordered C-terminal domain (CTD). In C. crescentus, the RNaseE CTD is necessary and sufficient to drive phase separation. In vivo RNaseE drives the formation of cytoplasmic foci that colocalize with other exonucleases. This degradation
Management of Phosphate Levels and Synthesis of Multivalent Phosphates
Bacteria utilize novel mechanisms to manage intracellular phosphate levels, particularly at times of nutrient deprivation. Under these conditions, bacteria will burn ATP to synthesize long polyphosphate (PolyP) chains that coalesce into large granules that are required for survival. These PolyP granules sequester certain proteins including the polyphosphate-synthesizing enzyme Ppk1 [117]. Polyphosphates are reminiscent of nucleic acid backbones and it appears that the physical principles
Concluding Remarks
We have focused on specific examples (Figure 3, Key Figure) to make the case that IDRs and biomolecular condensates have relevant and important roles to play in bacteria. In doing so, we have relied on the minimalist definition provided by Banani et al. [2] for designating membraneless bodies as condensates. Whether these condensates form and dissolve via spontaneous (passive) or driven (active) PSP transitions [54] will need to be resolved via systematic assessments in vitro and in vivo. There
Acknowledgments
This work was supported by grants to R.V.P. from the US National Science Foundation (MCB-1614766) and the Human Frontier Science Program (RGP0034/2017). We are grateful to Alex Holehouse, Keren Lasker, Petra Levin, Timothy Lohman, Kiersten Ruff, and Saumya Saurabh for critical reading of the manuscript and numerous stimulating discussions regarding IDRs in bacteria and their relevance to cellular regulation. R.V.P. acknowledges ongoing and engaging interactions with Simon Alberti, Clifford
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