Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Widespread distribution of encapsulin nanocompartments reveals functional diversity

Abstract

Cells organize and regulate their metabolism via membrane- or protein-bound organelles. In this way, incompatible processes can be spatially separated and controlled. In prokaryotes, protein-based compartments are used to sequester harmful reactions and store useful compounds. These protein compartments play key roles in various metabolic and ecological processes, ranging from iron homeostasis to carbon fixation. One of the newest types of protein organelle are encapsulin nanocompartments. They are able to encapsulate specific protein cargo and are proposed to be involved in redox-related processes. We identified more than 900 putative encapsulin systems in bacterial and archaeal genomes. Encapsulins can be found in fifteen bacterial and two archaeal phyla. Our analysis reveals one new capsid type and nine previously unknown cargo proteins targeted to the interior of encapsulins. We experimentally characterize three newly identified encapsulin systems and illustrate their probable involvement in iron mineralization, oxidative and nitrosative stress resistance and anaerobic ammonium oxidation, a process responsible for 30% of the nitrogen lost from the oceans.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Distribution, organization and diversity of encapsulin systems in prokaryotes.
Figure 2: Secondary cargo, associated components and diversity of Flp-like cargo in encapsulin systems.
Figure 3: Classification and characterization of encapsulin capsids.
Figure 4: Characterization of the Streptomyces sp. AA4 Haem encapsulin system involved in oxidative and nitrosative stress resistance.
Figure 5: Characterization of the Bacillaceae bacterium MTCC 10057 IMEF encapsulin system involved in iron mineralization.
Figure 6: Characterization of the encapsulin system in the anammox bacterium K. stuttgartiensis.

References

  1. 1

    Diekmann, Y. & Pereira-Leal, J. B. Evolution of intracellular compartmentalization. Biochem. J. 449, 319–331 (2013).

    CAS  Article  Google Scholar 

  2. 2

    Martin, W. Evolutionary origins of metabolic compartmentalization in eukaryotes. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 847–855 (2010).

    CAS  Article  Google Scholar 

  3. 3

    Schrader, M., Godinho, L. F., Costello, J. L. & Islinger, M. The different facets of organelle interplay—an overview of organelle interactions. Front. Cell Dev. Biol. 3, 56 (2015).

    Article  Google Scholar 

  4. 4

    Cornejo, E., Abreu, N. & Komeili, A. Compartmentalization and organelle formation in bacteria. Curr. Opin. Cell Biol. 26, 132–138 (2014).

    CAS  Article  Google Scholar 

  5. 5

    Giessen, T. W. & Silver, P. A. Encapsulation as a strategy for the design of biological compartmentalization. J. Mol. Biol. 428, 916–927 (2016).

    CAS  Article  Google Scholar 

  6. 6

    Kerfeld, C. A. & Erbilgin, O. Bacterial microcompartments and the modular construction of microbial metabolism. Trends Microbiol. 23, 22–34 (2015).

    CAS  Article  Google Scholar 

  7. 7

    Kerfeld, C. A. & Melnicki, M. R. Assembly, function and evolution of cyanobacterial carboxysomes. Curr. Opin. Plant Biol. 31, 66–75 (2016).

    CAS  Article  Google Scholar 

  8. 8

    Hintze, K. J. & Theil, E. C. Cellular regulation and molecular interactions of the ferritins. Cell. Mol. Life Sci. 63, 591–600 (2006).

    CAS  Article  Google Scholar 

  9. 9

    Pfeifer, F. Distribution, formation and regulation of gas vesicles. Nat. Rev. Microbiol. 10, 705–715 (2012).

    CAS  Article  Google Scholar 

  10. 10

    Chen, A. H., Robinson-Mosher, A., Savage, D. F., Silver, P. A. & Polka, J. K. The bacterial carbon-fixing organelle is formed by shell envelopment of preassembled cargo. PLoS ONE 8, e76127 (2013).

    CAS  Article  Google Scholar 

  11. 11

    Giessen, T. W. Encapsulins: microbial nanocompartments with applications in biomedicine, nanobiotechnology and materials science. Curr. Opin. Chem. Biol. 34, 1–10 (2016).

    CAS  Article  Google Scholar 

  12. 12

    Sutter, M. et al. Structural basis of enzyme encapsulation into a bacterial nanocompartment. Nat. Struct. Mol. Biol. 15, 939–947 (2008).

    CAS  Article  Google Scholar 

  13. 13

    Rurup, W. F., Snijder, J., Koay, M. S., Heck, A. J. & Cornelissen, J. J. Self-sorting of foreign proteins in a bacterial nanocompartment. J. Am. Chem. Soc. 136, 3828–3832 (2014).

    CAS  Article  Google Scholar 

  14. 14

    McHugh, C. A. et al. A virus capsid-like nanocompartment that stores iron and protects bacteria from oxidative stress. EMBO J. 33, 1896–1911 (2014).

    CAS  Article  Google Scholar 

  15. 15

    He, D. et al. Structural characterization of encapsulated ferritin provides insight into iron storage in bacterial nanocompartments. eLife 5, e18972 (2016).

    Article  Google Scholar 

  16. 16

    Akita, F. et al. The crystal structure of a virus-like particle from the hyperthermophilic archaeon Pyrococcus furiosus provides insight into the evolution of viruses. J. Mol. Biol. 368, 1469–1483 (2007).

    CAS  Article  Google Scholar 

  17. 17

    Rahmanpour, R. & Bugg, T. D. Assembly in vitro of Rhodococcus jostii RHA1 encapsulin and peroxidase DypB to form a nanocompartment. FEBS J. 280, 2097–2104 (2013).

    CAS  Article  Google Scholar 

  18. 18

    Valdes-Stauber, N. & Scherer, S. Isolation and characterization of Linocin M18, a bacteriocin produced by Brevibacterium linens. Appl. Environ. Microbiol. 60, 3809–3814 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Contreras, H. et al. Characterization of a Mycobacterium tuberculosis nanocompartment and its potential cargo proteins. J. Biol. Chem. 289, 18279–18289 (2014).

    CAS  Article  Google Scholar 

  20. 20

    Medema, M. H., Takano, E. & Breitling, R. Detecting sequence homology at the gene cluster level with MultiGeneBlast. Mol. Biol. Evol. 30, 1218–1223 (2013).

    CAS  Article  Google Scholar 

  21. 21

    Alvarez-Carreno, C., Becerra, A. & Lazcano, A. Molecular evolution of the oxygen-binding hemerythrin domain. PLoS ONE 11, e0157904 (2016).

    Article  Google Scholar 

  22. 22

    Li, X. et al. A bacterial hemerythrin-like protein MsmHr inhibits the SigF-dependent hydrogen peroxide response in mycobacteria. Front. Microbiol. 5, 800 (2014).

    PubMed  Google Scholar 

  23. 23

    Andrews, S. C. The ferritin-like superfamily: evolution of the biological iron storeman from a rubrerythrin-like ancestor. Biochim. Biophys. Acta 1800, 691–705 (2010).

    CAS  Article  Google Scholar 

  24. 24

    Kartal, B. et al. How to make a living from anaerobic ammonium oxidation. FEMS Microbiol. Rev. 37, 428–461 (2013).

    CAS  Article  Google Scholar 

  25. 25

    Radford, D. Understanding the Encapsulins: Prediction and Characterization of Phage Capsid-Like Nanocompartments in Prokaryotes. PhD thesis, Univ. Toronto (2015).

  26. 26

    Gerlt, J. A. et al. Enzyme function initiative-enzyme similarity tool (EFI-EST): a web tool for generating protein sequence similarity networks. Biochim. Biophys. Acta 1854, 1019–1037 (2015).

    CAS  Article  Google Scholar 

  27. 27

    Straub, K. L., Hanzlik, M. & Buchholz-Cleven, B. E. The use of biologically produced ferrihydrite for the isolation of novel iron-reducing bacteria. Syst. Appl. Microbiol. 21, 442–449 (1998).

    CAS  Article  Google Scholar 

  28. 28

    Hathazi, D. et al. Oxidative protection of hemoglobin and hemerythrin by cross-linking with a nonheme iron peroxidase: potentially improved oxygen carriers for use in blood substitutes. Biomacromolecules 15, 1920–1927 (2014).

    CAS  Article  Google Scholar 

  29. 29

    Okamoto, Y. et al. H2O2-dependent substrate oxidation by an engineered diiron site in a bacterial hemerythrin. Chem. Commun. 50, 3421–3423 (2014).

    CAS  Article  Google Scholar 

  30. 30

    Richards, F. A. in Chemical Oceanography Vol. 1 (eds Riley, J. P. and Skirrow, G. ) 611–645 (Academic Press, 1965).

    Google Scholar 

  31. 31

    Ward, B. B. & Jensen, M. M. The microbial nitrogen cycle. Front. Microbiol. 5, 553 (2014).

    Article  Google Scholar 

  32. 32

    Fuerst, J. A. & Sagulenko, E. Nested bacterial boxes: nuclear and other intracellular compartments in planctomycetes. J. Mol. Microbiol. Biotechnol. 23, 95–103 (2013).

    CAS  Article  Google Scholar 

  33. 33

    Javidpour, P. et al. Investigation of proposed ladderane biosynthetic genes from anammox bacteria by heterologous expression in E. coli. PLoS ONE 11, e0151087 (2016).

    Article  Google Scholar 

  34. 34

    Tsuda, A. et al. Structural and mechanistic insights into the electron flow through protein for cytochrome c-tethering copper nitrite reductase. J. Biochem. 154, 51–60 (2013).

    CAS  Article  Google Scholar 

  35. 35

    Mauerer, B., Crane, J., Schuler, J., Wieghardt, K. & Nuber, B. A hemerythrin model complex with catalase activity. Angew. Chem. Int. Ed. 32, 289–291 (1993).

    Article  Google Scholar 

  36. 36

    Wang, Y. et al. Characterization of the bacterioferritin/bacterioferritin associated ferredoxin protein–protein interaction in solution and determination of binding energy hot spots. Biochemistry 54, 6162–6175 (2015).

    CAS  Article  Google Scholar 

  37. 37

    Cozzi, A. et al. Overexpression of wild type and mutated human ferritin H-chain in HeLa cells: in vivo role of ferritin ferroxidase activity. J. Biol. Chem. 275, 25122–25129 (2000).

    CAS  Article  Google Scholar 

  38. 38

    Zhao, G. et al. Iron and hydrogen peroxide detoxification properties of DNA-binding protein from starved cells. A ferritin-like DNA-binding protein of Escherichia coli. J. Biol. Chem. 277, 27689–27696 (2002).

    CAS  Article  Google Scholar 

  39. 39

    Klotz, M. G. et al. Evolution of an octahaem cytochrome c protein family that is key to aerobic and anaerobic ammonia oxidation by bacteria. Environ. Microbiol. 10, 3150–3163 (2008).

    CAS  Article  Google Scholar 

  40. 40

    van Niftrik, L. et al. Combined structural and chemical analysis of the anammoxosome: a membrane-bounded intracytoplasmic compartment in anammox bacteria. J. Struct. Biol. 161, 401–410 (2008).

    CAS  Article  Google Scholar 

  41. 41

    Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).

    CAS  Article  Google Scholar 

  42. 42

    Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).

    Article  Google Scholar 

  43. 43

    Letunic, I. & Bork, P. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 44, W242–W245 (2016).

    CAS  Article  Google Scholar 

  44. 44

    Petersen, T. N., Brunak, S., von Heijne, G. & Nielsen, H. Signalp 4.0: discriminating signal peptides from transmembrane regions. Nat. Methods 8, 785–786 (2011).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by a Leopoldina Research Fellowship (LPDS 2014-05) from the German National Academy of Sciences Leopoldina (T.W.G), the DARPA Living Foundries 1000 Molecules grant (award no. HR0011-14-C-0072, to P.A.S) and the Wyss Institute for Biologically Inspired Engineering at Harvard University (to T.W.G and P.A.S). The authors thank A. Chan and J. Hegemann for thoughtful comments on the manuscript.

Author information

Affiliations

Authors

Contributions

T.W.G. and P.A.S designed the research and wrote the paper. T.W.G. performed experiments.

Corresponding author

Correspondence to Pamela A. Silver.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary Table 2, Supplementary Figures 1–9 (PDF 4071 kb)

Supplementary Table 1

List of identified encapsulin systems (XLSX 88 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Giessen, T., Silver, P. Widespread distribution of encapsulin nanocompartments reveals functional diversity. Nat Microbiol 2, 17029 (2017). https://doi.org/10.1038/nmicrobiol.2017.29

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing