Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012:28:89-111.
doi: 10.1146/annurev-cellbio-101011-155841.

Dynamic reorganization of metabolic enzymes into intracellular bodies

Jeremy D O'Connell  1 , Alice Zhao, Andrew D Ellington, Edward M Marcotte
Affiliations
Review

Dynamic reorganization of metabolic enzymes into intracellular bodies

Jeremy D O'Connell et al. Annu Rev Cell Dev Biol. 2012.

Abstract

Both focused and large-scale cell biological and biochemical studies have revealed that hundreds of metabolic enzymes across diverse organisms form large intracellular bodies. These proteinaceous bodies range in form from fibers and intracellular foci--such as those formed by enzymes of nitrogen and carbon utilization and of nucleotide biosynthesis--to high-density packings inside bacterial microcompartments and eukaryotic microbodies. Although many enzymes clearly form functional mega-assemblies, it is not yet clear for many recently discovered cases whether they represent functional entities, storage bodies, or aggregates. In this article, we survey intracellular protein bodies formed by metabolic enzymes, asking when and why such bodies form and what their formation implies for the functionality--and dysfunctionality--of the enzymes that comprise them. The panoply of intracellular protein bodies also raises interesting questions regarding their evolution and maintenance within cells. We speculate on models for how such structures form in the first place and why they may be inevitable.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Bacterial microcompartments as exemplified by carboxysomes. (a) Transmission electron micrographs of Halothiobacillus neapolitanus cells showing carboxysomes (arrows) as polyhedral, protein-dense bodies. Adapted from Yeates et al. (2007). (b) The major shell protein (CsoS1ABC in H. neapolitanus) is a hexagonal subunit that oligomerizes into massive sheets that are bent into joined facets at the vertices by a second, pentagonal protein (CsoS4AB) to complete the shell. The interior of the shell is packed with RuBisCO and carbonic anhydrase to maximize CO2 capture. Adapted from Bonacci et al. (2011). (c) Fluorescence microscopy of carboxysomes (green) shows that their in vivo location within cyanobacteria is regulated such that they are centrally aligned and evenly spaced roughly 0.5 μm apart. Adapted from Savage et al. (2010).
Figure 2
Figure 2
Examples of microbodies visualized by thin-section transmission electron microscopy. (a) Peroxisomes (arrow) within sunflower cotyledon mesophyll cells. Crystalline inclusion bodies are formed from catalase, as shown by the immunogold nanoparticle localization (black dots). Adapted from Tenberge & Eising (1995) and Pavelka & Roth (2010). (b) Aspergillus nidulans showing a Woronin body filled with a HEX-1 protein crystal. Adapted from Yuan et al. (2003). Abbreviations: C, crystalline inclusion bodies; PM, peroxisomal matrix.
Figure 3
Figure 3
Green fluorescent protein C-terminal cytidine triphosphate (GFP-CTP) synthase fibers within Drosophila egg chamber cells. The fibers exhibit a diverse range of lengths. Adapted from Liu (2010).
Figure 4
Figure 4
Hundreds of foci- and fiber-forming proteins have been discovered in systematic protein localization screens; most of these intracellular bodies are still largely uncharacterized. (a,b) Representative foci (ACCase β-subunit)- and fiber (UDP-N-acetylmuramate-alanine ligase)-forming green fluorescent protein (GFP) fusion proteins, respectively, from Caulobacter crescentus. Adapted from Werner et al. (2009). (c,d) Representative foci (Ade4)- and fiber (Pil1)-forming yellow fluorescent protein-fusion proteins, respectively, from Schizosaccharomyces pombe. Adapted from Matsuyama et al. (2006). (e,f) Representative foci (Gln1p)- and fiber (Asn2p)-forming GFP-fusion proteins, respectively, from Saccharomyces cerevisiae. Adapted from Narayanaswamy et al. (2009).
Figure 5
Figure 5
Proteins that assemble into symmetric quaternary structures should in principle have a higher propensity to form fibers, because effectors, whether allosteric, covalent, or mutational, that enhance binding between the oligomeric faces may be multiplied around the axis of symmetry, leading to enhanced fiber stability. The types of effectors and their contribution to fiber stability or destabilization can inform about an enzymatic fiber’s role within cells.
Figure 6
Figure 6
A sampling of metabolic enzymes that self-assemble into fibers. The quaternary structure of each enzyme is illustrated schematically (top row), following 90° rotation (middle row), and imaged in fiber form by electron microscopy (bottom row). (a) Acetyl-CoA carboxylase: crystal structure of Streptomyces coelicolor acetyl-CoA carboxylase β-subunit, PDB ID: 1XO6 (Diacovich et al. 2004) and electron micrograph of rat liver acetyl-CoA carboxylase (Nelson et al. 2008). (b) β-glucosidase: crystal structure of wheat β-glucosidase, PDB ID: 2DGA (Sue et al. 2006), and electron micrograph of oat β-glucosidase (Kim et al. 2005). (c) Glutamine synthetase: crystal structure of Escherichia coli glutamine synthetase, PDB ID: 1FY (Gill & Eisenberg 2001), and electron micrograph of E. coli glutamine synthetase (Frey et al. 1975). (d) Glutamate dehydrogenase: crystal structure of Clostridium symbiosum glutamate dehydrogenase, PDB ID: 1BGV (Stillman et al. 1993), and electron micrograph of cow liver glutamate dehydrogenase (Josephs & Borisy 1972). Scale not provided. (e) CTP synthase: human CTP synthase 2, PDB ID: 3IHL (M. Moche et al., unpublished data), and electron micrograph of Drosophila CTP synthase (Liu 2010). (f) Inosine monophosphate dehydrogenase: crystal structure of human type II inosine monophosphate dehydrogenase, PDB ID: 1NF7 (D. Risal, M.D. Strickler, B.M. Goldstein, unpublished data), and electron micrograph of human type II inosine monophosphate dehydrogenase (Ingerson-Mahar et al. 2010). (g) Human sickle-cell mutant hemoglobin: crystal structure, PDB ID: 2HBS (Harrington et al. 1997), and electron micrograph human sickle-cell mutant hemoglobin: (Ohtsuki et al. 1977). All crystal structure images created with Jmol.
Figure 7
Figure 7
An illustration of the analogous effects on cell morphology by cytidine triphosphate (CTP) synthase and sickle-cell mutant hemoglobin (HbS). (a) Bright field images of Caulobacter crescentus cells depleted of CTP synthase show severe bending, some to the point of circularization. (b) Cells overexpressing CTP synthase are straightened markedly. (c) Transmission electron micrograph of a C. crescentus cell with CTP synthase fibers (arrows) along the cell wall, altering cell morphology. Panels a–c adapted from Ingerson-Mahar et al. (2010). (d) Analogous images of red blood cells showing their normal, round morphology when oxygenated, and (e) their highly straightened morphology when the deoxygenated HbS forms into fibers. Adapted from Kaul et al. (1983). (f) Transmission electron micrograph showing HbS fibers (arrows) along the cell walls, altering cell morphology. Adapted from Döbler & Bertles (1968).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, et al. Structural conversion of neurotoxic amyloid-β1–42 oligomers to fibrils. Nat. Struct. Mol. Biol. 2010;17(5):561–67. - PMC - PubMed
    1. Alberti S, Halfmann R, King O, Kapila A, Lindquist S. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell. 2009;137(1):146–58. - PMC - PubMed
    1. An S, Deng Y, Tomsho JW, Kyoung M, Benkovic SJ. Microtubule-assisted mechanism for functional metabolic macromolecular complex formation. Proc. Natl. Acad. Sci. USA. 2010a;107(29):12872–76. - PMC - PubMed
    1. An S, Kumar R, Sheets ED, Benkovic SJ. Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science. 2008;320(5872):103–6. - PubMed
    1. An S, Kyoung M, Allen JJ, Shokat KM, Benkovic SJ. Dynamic regulation of a metabolic multi-enzyme complex by protein kinase CK2. J. Biol. Chem. 2010b;285(15):11093–99. - PMC - PubMed

Publication types

LinkOut - more resources