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

Fingerprint

Plasmids
Adenosine Triphosphatases
DNA
Bacteria
Proteins
Microtubules
Cell Division
Actins
Theoretical Models

Keywords

  • Brownian ratchet
  • Motility
  • Para atpase
  • Theoretical model

ASJC Scopus subject areas

  • General

Cite this

Directed and persistent movement arises from mechanochemistry of the ParA/ParB system. / Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 51, 22.12.2015, p. E7055-E7064.

Research output: Contribution to journalArticle

Hu, Longhua ; Vecchiarelli, Anthony G. ; Mizuuchi, Kiyoshi ; Neuman, Keir C. ; Liu, Jian. / Directed and persistent movement arises from mechanochemistry of the ParA/ParB system. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 51. pp. E7055-E7064.
@article{d555d1e2ecc0485a8f82b33e361d7f86,
title = "Directed and persistent movement arises from mechanochemistry of the ParA/ParB system",
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.",
keywords = "Brownian ratchet, Motility, Para atpase, Theoretical model",
author = "Longhua Hu and Vecchiarelli, {Anthony G.} and Kiyoshi Mizuuchi and Neuman, {Keir C.} and Jian Liu",
year = "2015",
month = "12",
day = "22",
doi = "10.1073/pnas.1505147112",
language = "English (US)",
volume = "112",
pages = "E7055--E7064",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "51",

}

TY - JOUR

T1 - Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

AU - Hu, Longhua

AU - Vecchiarelli, Anthony G.

AU - Mizuuchi, Kiyoshi

AU - Neuman, Keir C.

AU - Liu, Jian

PY - 2015/12/22

Y1 - 2015/12/22

N2 - 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.

AB - 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.

KW - Brownian ratchet

KW - Motility

KW - Para atpase

KW - Theoretical model

UR - http://www.scopus.com/inward/record.url?scp=84952651301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952651301&partnerID=8YFLogxK

U2 - 10.1073/pnas.1505147112

DO - 10.1073/pnas.1505147112

M3 - Article

C2 - 26647183

AN - SCOPUS:84952651301

VL - 112

SP - E7055-E7064

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 51

ER -