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Uncoupling of nucleotide hydrolysis and polymerization in the ParA protein superfamily disrupts DNA segregation dynamics.

Publication ,  Journal Article
Dobruk-Serkowska, A; Caccamo, M; Rodríguez-Castañeda, F; Wu, M; Bryce, K; Ng, I; Schumacher, MA; Barillà, D; Hayes, F
Published in: J Biol Chem
December 14, 2012

DNA segregation in bacteria is mediated most frequently by proteins of the ParA superfamily that transport DNA molecules attached via the segrosome nucleoprotein complex. Segregation is governed by a cycle of ATP-induced polymerization and subsequent depolymerization of the ParA factor. Here, we establish that hyperactive ATPase variants of the ParA homolog ParF display altered segrosome dynamics that block accurate DNA segregation. An arginine finger-like motif in the ParG centromere-binding factor augments ParF ATPase activity but is ineffective in stimulating nucleotide hydrolysis by the hyperactive proteins. Moreover, whereas polymerization of wild-type ParF is accelerated by ATP and inhibited by ADP, filamentation of the mutated proteins is blocked indiscriminately by nucleotides. The mutations affect a triplet of conserved residues that are situated neither in canonical nucleotide binding and hydrolysis motifs in the ParF tertiary structure nor at interfaces implicated in ParF polymerization. Instead the residues are involved in shaping the contours of the binding pocket so that nucleotide binding locks the mutant proteins into a configuration that is refractory to polymerization. Thus, the architecture of the pocket not only is crucial for optimal ATPase kinetics but also plays a key role in the polymerization dynamics of ParA proteins that drive DNA segregation ubiquitously in procaryotes.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

December 14, 2012

Volume

287

Issue

51

Start / End Page

42545 / 42553

Location

United States

Related Subject Headings

  • Protein Binding
  • Polymerization
  • Nucleotides
  • Mutation
  • Mutant Proteins
  • Multigene Family
  • Molecular Sequence Data
  • Kinetics
  • Hydrolysis
  • Fluorescence Polarization
 

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Dobruk-Serkowska, A., Caccamo, M., Rodríguez-Castañeda, F., Wu, M., Bryce, K., Ng, I., … Hayes, F. (2012). Uncoupling of nucleotide hydrolysis and polymerization in the ParA protein superfamily disrupts DNA segregation dynamics. J Biol Chem, 287(51), 42545–42553. https://doi.org/10.1074/jbc.M112.410324
Dobruk-Serkowska, Aneta, Marisa Caccamo, Fernando Rodríguez-Castañeda, Meiyi Wu, Kerstyn Bryce, Irene Ng, Maria A. Schumacher, Daniela Barillà, and Finbarr Hayes. “Uncoupling of nucleotide hydrolysis and polymerization in the ParA protein superfamily disrupts DNA segregation dynamics.J Biol Chem 287, no. 51 (December 14, 2012): 42545–53. https://doi.org/10.1074/jbc.M112.410324.
Dobruk-Serkowska A, Caccamo M, Rodríguez-Castañeda F, Wu M, Bryce K, Ng I, et al. Uncoupling of nucleotide hydrolysis and polymerization in the ParA protein superfamily disrupts DNA segregation dynamics. J Biol Chem. 2012 Dec 14;287(51):42545–53.
Dobruk-Serkowska, Aneta, et al. “Uncoupling of nucleotide hydrolysis and polymerization in the ParA protein superfamily disrupts DNA segregation dynamics.J Biol Chem, vol. 287, no. 51, Dec. 2012, pp. 42545–53. Pubmed, doi:10.1074/jbc.M112.410324.
Dobruk-Serkowska A, Caccamo M, Rodríguez-Castañeda F, Wu M, Bryce K, Ng I, Schumacher MA, Barillà D, Hayes F. Uncoupling of nucleotide hydrolysis and polymerization in the ParA protein superfamily disrupts DNA segregation dynamics. J Biol Chem. 2012 Dec 14;287(51):42545–42553.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

December 14, 2012

Volume

287

Issue

51

Start / End Page

42545 / 42553

Location

United States

Related Subject Headings

  • Protein Binding
  • Polymerization
  • Nucleotides
  • Mutation
  • Mutant Proteins
  • Multigene Family
  • Molecular Sequence Data
  • Kinetics
  • Hydrolysis
  • Fluorescence Polarization