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The ParMRC system: molecular mechanisms of plasmid segregation by actin-like filaments

Key Points

  • ParMRC is an independent DNA segregation system that is carried by some low-copy-number plasmids and is sufficient to ensure that plasmids are not lost during host cell division.

  • ParMRC is composed of just three components: a filament-forming, actin-like ATPase motor (ParM), a DNA-binding adaptor (ParR) and a centromere-like DNA region (parC).

  • Plasmid segregation is driven by ParM filaments, which are dynamically unstable unless capped at both ends by a plasmid-bound ParR–parC complex. Once stabilized, ParM filaments move the attached plasmids in opposite directions, so driving the DNA apart.

  • ParM filaments assemble into small bundles in the cell, and these probably move clusters of plasmids apart. There are no known host cell factors required for segregation.

  • ParM is structurally related to eukaryotic actin and forms similar ATP-dependent double filaments, although the filaments wrap around one another with opposite handedness. Despite the structural similarity, the dynamics of ParM have three unique characteristics that differ from those of actin dynamics: equal bipolar elongation, dynamic instability and a high rate of spontaneous nucleation. These properties are tuned to enable ParM filaments to search the cell space for plasmid-bound ParR–parC complexes using a 'search and capture' mechanism.

  • The ParR–parC nucleoprotein cap forms a large solenoid structure that binds to the very tips of ParM filaments and prevents filament disassembly. The exact structure and molecular mechanism of this complex are unknown.

Abstract

The ParMRC plasmid partitioning apparatus is one of the best characterized systems for bacterial DNA segregation. Bundles of actin-like filaments are used to push plasmids to opposite poles of the cell, whereupon they are stably inherited on cell division. This plasmid-encoded system comprises just three components: an actin-like protein, ParM, a DNA-binding adaptor protein, ParR, and a centromere-like region, parC. The properties and interactions of these components have been finely tuned to enable ParM filaments to search the cell space for plasmids and then move ParR–parC-bound DNA molecules apart. In this Review, we look at some of the most exciting questions in the field concerning the exact molecular mechanisms by which the components of this self-contained system modulate one another's activity to achieve bipolar DNA segregation.

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Figure 1: An overview of the plasmid R1-encoded ParMRC plasmid segregation system.
Figure 2: The structure and properties of ParM.
Figure 3: The ParR–parC complex and its interaction with ParM filaments.

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Acknowledgements

The authors are grateful to K. Gerdes for helpful comments on the manuscript and to J. Møller-Jensen for ongoing collaborations.

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Protein Data Bank

Glossary

Walker A protein

Protein that contains a Walker A motif (GXXXGKT; where X is any amino acid), and is involved in the nucleotide binding of many ATP-requiring enzymes.

Tubulin

Basic subunit of microtubules. Tubulin comes in two forms, α-tubulin and β-tubulin, which form heterodimers that make up microtubules.

Filamentous actin

Flexible, helical polymer of G-actin monomers that is 5–9nm in diameter. This polymer is polar, displaying a plus end and a minus end.

Microtubule

Hollow tube, 25nm in diameter, that is formed by the lateral association of 13 protofilaments, which are themselves polymers of α-tubulin and β-tubulin subunits.

Cofilin

Actin-binding protein that promotes disassembly at the minus ends of actin filaments.

Barbed end

The plus end of the polar F-actin polymer, which is more active than the minus end with regard to the incorporation of G-actin into the polymer.

Magnetosome

Unique intracellular structure that is found in magnetotactic bacteria and comprises a magnetic mineral crystal surrounded by a lipid bilayer membrane.

Nucleoid

Distinct region in the bacterial cytoplasm that harbours the chromosomal DNA.

Formin

Protein that contains a formin homology 2 (FH2) domain and promotes actin assembly. Formin binds to the ends of actin filaments.

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Salje, J., Gayathri, P. & Löwe, J. The ParMRC system: molecular mechanisms of plasmid segregation by actin-like filaments. Nat Rev Microbiol 8, 683–692 (2010). https://doi.org/10.1038/nrmicro2425

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