Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

Longhua Hu, Anthony G. Vecchiarelli, Kiyoshi Mizuuchi, Keir C. Neuman, Jian Liu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)E7055-E7064
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number51
DOIs
StatePublished - Dec 22 2015
Externally publishedYes

Keywords

  • Brownian ratchet
  • Motility
  • Para atpase
  • Theoretical model

ASJC Scopus subject areas

  • General

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