Beyond the cytoskeleton: mesoscale assemblies and their function in spatial organization

doi:10.1016/j.mib.2013.03.008

Current Opinion in Microbiology

Volume 16, Issue 2, April 2013, Pages 177-183

https://doi.org/10.1016/j.mib.2013.03.008 Get rights and content

Highlights

•
New imaging methods have lead to the discovery of a number of mesoscale protein assemblies.
•
Mesoscale assemblies enable the spatial organization of processes within the cell.
•
In addition to classic protein polymers dynamic phase-separated bodies also serve as spatial organizers.
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Mesoscale assemblies have a variety of functions related to metabolism.
•
The engineering of metabolic enzyme assemblies will lead to a variety of benefits.

Recent studies have identified a growing number of mesoscale protein assemblies in both bacterial and eukaryotic cells. Traditionally, these polymeric assemblies are thought to provide structural support for the cell and thus have been classified as the cytoskeleton. However a new class of macromolecular structure is emerging as an organizer of cellular processes that occur on scales hundreds of times larger than a single protein. We propose two types of self-assembling structures, dynamic globules and crystalline scaffolds, and suggest they provide a means to achieve cell-scale order. We discuss general mechanisms for assembly and regulation. Finally, we discuss assemblies that are found to organize metabolism and what possible mechanisms may serve these metabolic enzyme complexes.

Introduction

A cell's ability to coordinate the spatial arrangement of its components is crucial for it to achieve functional complexity. Eukaryotes have, partly, achieved this complexity by isolating specific reactions into membrane bound organelles. Similarly, gram-negative prokaryotes use both inner and outer membranes to compartmentalize their cytoplasm and periplasm. However, generating membrane bound compartments de novo is a cumbersome process, and even the most complex cells have a limited number of distinct types of organelles. An alternative strategy is for proteins to organize into distinct assemblies, enabling cells to establish functionally differentiated subcellular regions even in the absence of membrane barriers. While bacteria generally lack membrane-bound organelles, recent evidence suggests that the cytoplasms of both bacterial and eukaryotic cells are highly organized by such protein assemblies [1].

Higher-order protein assemblies exist in a mesoscale between the nanoscale of individual proteins and the microscale of whole cells (Figure 1). To occupy this mesoscale, assemblies are often constructed from one or more types of repeating nanoscale subunit. This feature is advantageous because it enables construction of large structures using only a small number of genes (genetic efficiency) and it is amenable to regulation and quality control by exclusion of malformed subunits [2]. Once assembled, these structures typically extend as polymers that form filaments or sheets, hundreds of times larger than an individual monomer. Multiple polymers can also be densely interconnected (crosslinked) to form dynamic, phase-separated globules or bodies. Here we highlight the recent appreciation that mesoscale protein assemblies are much more common than previously thought and we review some of their emerging forms, how they are regulated, and some of their newly attributed organizing functions. We then focus on how new discoveries about mesoscale assemblies are changing our ability to both understand and manipulate even one of the most well-studied biological networks, metabolism.

Section snippets

New organizing functions for macromolecular assemblies

A wealth of macromolecular structures has recently been discovered largely due to new imaging techniques and an increase in our ability to perform high-throughput screens. Genome-wide fluorescent labeling screens in both eukaryotes and prokaryotes have only begun to enumerate the wide assortment of protein assemblies [3, 4]. Electron cryotomography (ECT) complemented by genetics has further aided in defining their various shapes. Filaments, rings, sheets, lattices and tubes have all been

Phase-separated assemblies as dynamic organizing structures

In addition to the canonical, rigid, self-assembling macromolecular polymers discussed above, an emerging physical class of mesoscale structures form assemblies that undergo a liquid-like phase transition, essentially generating phase-separated microdomains in the absence of membrane barriers. For example, the Caenorhabditis elegans P granule is a structure containing a large number of RNAs and RNA-binding proteins that forms visually distinct globules with physical properties similar to a

Coordinating metabolism with mesoscale assemblies

One aspect of cellular physiology for which mesoscale assemblies appear to have particular significance is metabolism. Metabolism is classically thought of as a well-mixed spatially distributed process. However, new studies are identifying large numbers of metabolic enzymes as members of mesoscale assemblies [4, 31, 32, 33] suggesting that metabolism may benefit from mesoscale spatial organization. The most straightforward function for spatial organization in metabolism is to bring together

Conclusion

Here we highlight the self-assembling, mesoscale structures as a general mechanism for organizing biological functions. Not only does life utilize multimeric assembly as a rapid and efficient method of bridging the nanoscale to the microscale, but it also enables the coupling of time and space through the kinetics of assembly. Recently discovered examples of polymeric proteins and phase-separated liquid droplets suggest that both eukaryotic and prokaryotic cells abound with these mesoscale

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

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View full text

Beyond the cytoskeleton: mesoscale assemblies and their function in spatial organization

Highlights

Introduction

Section snippets

New organizing functions for macromolecular assemblies

Phase-separated assemblies as dynamic organizing structures

Coordinating metabolism with mesoscale assemblies

Conclusion

References and recommended reading

Cell

Cell

J Bacteriol

Science

Cell

Cell

Cell

Science

Cold Spring Harb Symp Quant Biol

J Biol Chem

J Biol Chem

Arch Biochem Biophys

Nat Rev Micro

Science

Nat Biotechnol

Why and how bacteria localize proteins

Science

Molecular Biology of the Cell

Quantitative genome-scale analysis of protein localization in an asymmetric bacterium

Proc Natl Acad Sci U S A

Widespread reorganization of metabolic enzymes into reversible assemblies upon nutrient starvation

Proc Natl Acad Sci U S A

The bacterial cytoskeleton: more than twisted filaments

Curr Opin Cell Biol

Determination of bacterial rod shape by a novel cytoskeletal membrane protein

EMBO J

YeeV is an Escherichia coli toxin that inhibits cell division by targeting the cytoskeleton proteins, FtsZ and MreB

Mol Microbiol

A polymeric protein anchors the chromosomal origin/ParB Complex at a bacterial cell pole

Cell