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

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.

[1]  Pamela A Silver,et al.  Designing biological compartmentalization. , 2012, Trends in cell biology.

[2]  G. Jensen,et al.  The metabolic enzyme CTP synthase forms cytoskeletal filaments , 2010, Nature Cell Biology.

[3]  T. Selwood,et al.  Dynamic dissociating homo-oligomers and the control of protein function. , 2012, Archives of biochemistry and biophysics.

[4]  William C. Deloache,et al.  Spatial organization of enzymes for metabolic engineering. , 2012, Metabolic engineering.

[5]  T. Bobik,et al.  Microcompartments for B12-Dependent 1,2-Propanediol Degradation Provide Protection from DNA and Cellular Damage by a Reactive Metabolic Intermediate , 2008, Journal of bacteriology.

[6]  D. Spector,et al.  SnapShot: Cellular Bodies , 2006, Cell.

[7]  M. Dundr,et al.  Nucleation of nuclear bodies by RNA , 2011, Nature Cell Biology.

[8]  K. Praveen,et al.  Genetic analysis of nuclear bodies: from nondeterministic chaos to deterministic order. , 2010, Cold Spring Harbor symposia on quantitative biology.

[9]  K. Shokat,et al.  Dynamic Regulation of a Metabolic Multi-enzyme Complex by Protein Kinase CK2 , 2010, The Journal of Biological Chemistry.

[10]  Kenneth S Kosik,et al.  Neuronal RNA Granules A Link between RNA Localization and Stimulation-Dependent Translation , 2001, Neuron.

[11]  J. Irgon,et al.  Quantitative genome-scale analysis of protein localization in an asymmetric bacterium , 2009, Proceedings of the National Academy of Sciences.

[12]  Faisal A. Aldaye,et al.  Organization of Intracellular Reactions with Rationally Designed RNA Assemblies , 2011, Science.

[13]  G. Jensen,et al.  The bacterial cytoskeleton: more than twisted filaments. , 2013, Current opinion in cell biology.

[14]  Stephen J Benkovic,et al.  Reversible Compartmentalization of de Novo Purine Biosynthetic Complexes in Living Cells , 2008, Science.

[15]  T. Pawson,et al.  Assembly of Cell Regulatory Systems Through Protein Interaction Domains , 2003, Science.

[16]  G. Jensen,et al.  General Protein Diffusion Barriers Create Compartments within Bacterial Cells , 2012, Cell.

[17]  Gabriel C. Wu,et al.  Synthetic protein scaffolds provide modular control over metabolic flux , 2009, Nature Biotechnology.

[18]  Hao Wu,et al.  Structural Insights into the Assembly of Large Oligomeric Signalosomes in the Toll-Like Receptor–Interleukin-1 Receptor Superfamily , 2012, Science Signaling.

[19]  Jimin Pei,et al.  Cell-free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within Hydrogels , 2012, Cell.

[20]  G. Jensen,et al.  A Self-Associating Protein Critical for Chromosome Attachment, Division, and Polar Organization in Caulobacter , 2008, Cell.

[21]  Brian K. Sato,et al.  Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster , 2010, The Journal of cell biology.

[22]  J. Errington,et al.  Large ring polymers align FtsZ polymers for normal septum formation , 2011, The EMBO journal.

[23]  H. Muller Function of the Ocelli of Hymenopterous Insects , 1875 .

[24]  M. Inouye,et al.  YeeV is an Escherichia coli toxin that inhibits cell division by targeting the cytoskeleton proteins, FtsZ and MreB , 2011, Molecular microbiology.

[25]  H H McAdams,et al.  Why and How Bacteria Localize Proteins , 2009, Science.

[26]  C. Brangwynne,et al.  Getting RNA and Protein in Phase , 2012, Cell.

[27]  B. Golinelli‐Pimpaneau,et al.  Structural Basis for Morpheein-type Allosteric Regulation of Escherichia coli Glucosamine-6-phosphate Synthase , 2012, The Journal of Biological Chemistry.

[28]  G. Baillie Compartmentalized signalling: spatial regulation of cAMP by the action of compartmentalized phosphodiesterases , 2009, The FEBS journal.

[29]  L. Shapiro,et al.  A Polymeric Protein Anchors the Chromosomal Origin/ParB Complex at a Bacterial Cell Pole , 2008, Cell.

[30]  M. Dundr,et al.  De Novo Formation of a Subnuclear Body , 2008, Science.

[31]  Jimin Pei,et al.  Cell-free Formation of RNA Granules: Bound RNAs Identify Features and Components of Cellular Assemblies , 2012, Cell.

[32]  Pamela A Silver,et al.  Natural strategies for the spatial optimization of metabolism in synthetic biology. , 2012, Nature chemical biology.

[33]  M. Dundr,et al.  Nuclear bodies: multifunctional companions of the genome. , 2012, Current opinion in cell biology.

[34]  Paul S. Russo,et al.  Phase Transitions in the Assembly of MultiValent Signaling Proteins , 2016 .

[35]  Leigh G. Monahan,et al.  Lateral FtsZ association and the assembly of the cytokinetic Z ring in bacteria , 2009, Molecular microbiology.

[36]  J. Leong,et al.  Bacterial Scaffolds Assemble Novel Higher-Order Complexes to Reengineer Eukaryotic Cell Processes , 2011, Science Signaling.

[37]  Wendell A. Lim,et al.  Scaffold Proteins: Hubs for Controlling the Flow of Cellular Information , 2011, Science.

[38]  S. Benkovic,et al.  Mapping Protein-Protein Proximity in the Purinosome* , 2012, The Journal of Biological Chemistry.

[39]  Andrew D. Ellington,et al.  Widespread reorganization of metabolic enzymes into reversible assemblies upon nutrient starvation , 2009, Proceedings of the National Academy of Sciences.

[40]  E. Domenici,et al.  Characterization of divIVA and Other Genes Located in the Chromosomal Region Downstream of the dcw Cluster in Streptococcus pneumoniae , 2003, Journal of bacteriology.

[41]  S. Benkovic,et al.  Microtubule-assisted mechanism for functional metabolic macromolecular complex formation , 2010, Proceedings of the National Academy of Sciences.

[42]  H. Niki,et al.  Determination of bacterial rod shape by a novel cytoskeletal membrane protein , 2008, The EMBO journal.

[43]  J. Allen Development and application of technologies to study individual kinase substrate relationships , 2008 .

[44]  Mojca Benčina,et al.  DNA-guided assembly of biosynthetic pathways promotes improved catalytic efficiency , 2011, Nucleic acids research.

[45]  T. Yeates,et al.  Protein-based organelles in bacteria: carboxysomes and related microcompartments , 2008, Nature Reviews Microbiology.

[46]  A. Hyman,et al.  Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation , 2009, Science.

[47]  L. Hamoen,et al.  SepF, a novel FtsZ‐interacting protein required for a late step in cell division , 2006, Molecular microbiology.