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Directed and persistent movement arises from mechanochemistry of the ParA/ParB system
Longhua Hu1, Anthony G Vecchiarelli2, Kiyoshi Mizuuchi2
1Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892;
Abstract:
The segregation of DNA before cell division is essential for faithful genetic inheritance. In many bacteria, segregation of low-copy number plasmids involves an active partition system composed of a nonspecific DNA-binding ATPase, ParA, and its stimulator protein ParB. The ParA/ParB system drives directed and persistent movement of DNA cargo both in vivo and in vitro. Filament-based models akin to actin/microtubule-driven motility were proposed for plasmid segregation mediated by ParA. Recent experiments challenge this view and suggest that ParA/ParB system motility is driven by a diffusion ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. Here, we develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB-bound cargo. Paradoxically, this resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work thus sheds light on an emergent phenomenon in which nonmotor proteins work collectively via mechanochemical coupling to propel cargos-an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.
Insights
The bacterial ParA/ParB system drives DNA segregation using a diffusion ratchet mechanism. This process relies on transient protein tethers, enabling directed plasmid movement without traditional motor proteins.
Area of Science:
- Molecular Biology
- Microbiology
- Biophysics
Background:
- Faithful genetic inheritance relies on precise DNA segregation before cell division.
- Bacterial low-copy number plasmids utilize the ParA/ParB partition system for segregation.
- Previous models proposed filament-based motility for ParA/ParB, but recent data suggest a diffusion ratchet mechanism.
Purpose of the Study:
- To develop a theoretical model for ParA/ParB-mediated DNA motility.
- To elucidate the detailed mechanism driving directed and persistent movement of DNA cargo.
- To understand how nonmotor proteins collectively propel DNA in bacteria.
Main Methods:
- Theoretical modeling of the ParA/ParB system.
- Analysis of ATPase-dependent cycling of ParA-nucleoid affinity.
- Investigation of transient tethering to the nucleoid surface.
Main Results:
- The ParA/ParB system functions as a Brownian ratchet.
- Mechanochemical coupling drives directed motion of ParB-bound cargo.
- Processive motion results from quenching diffusion via numerous transient tethers.
Conclusions:
- The ParA/ParB system provides an evolutionary solution for DNA segregation in bacteria lacking processive motor proteins.
- Collective action of nonmotor proteins via mechanochemical coupling propels DNA cargo.
- The diffusion ratchet mechanism explains directed plasmid movement on the nucleoid surface.
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