Subunit Rtt102 controls the conformation of the Arp7/9 heterodimer and its interactions with nucleotide and the catalytic subunit of SWI/SNF remodelers

J Biol Chem. 2013 Dec 13;288(50):35758-68. doi: 10.1074/jbc.M113.514083. Epub 2013 Nov 4.

Abstract

Chromatin-remodeling complexes are assembled around a catalytic subunit that contains a central ATPase domain and flanking sequences that recruit auxiliary subunits. The catalytic subunits of SWI/SNF remodelers recruit Arp7/9 through a helicase/SANT-associated (HSA) domain N-terminal to the ATPase domain. Arp7/9-containing remodelers also carry the auxiliary subunit Rtt102, but the role of this subunit is poorly understood. Here, we show that Rtt102 binds with nanomolar affinity to the Arp7/9 heterodimer and modulates its conformation and interactions with the ATPase subunit and nucleotide. When bound to Rtt102, Arp7/9 interacts with a shorter segment of the HSA domain. Structural analysis by small-angle x-ray scattering further shows that when bound to Rtt102, the complex of Arp7/9 with the catalytic subunit assumes a more stable compact conformation. We also found that Arp7, Arp9, and Arp7/9 interact very weakly with ATP, but Rtt102 promotes high-affinity ATP binding to a single site in the heterodimer. Collectively, the results establish a function for subunit Rtt102 as a stabilizing factor for the Arp7/9 heterodimer, enhancing its interaction with nucleotide and controlling the conformation of SWI/SNF remodelers in an Arp7/9-dependent manner.

Keywords: ATP; Actin; Actin-related Proteins; Chromatin Remodeling; Isothermal Titration Calorimetry; Nucleotide Binding; Protein-Protein interactions; X-ray Scattering.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Carrier Proteins / metabolism*
  • Catalytic Domain*
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleosomes / genetics*
  • Protein Binding
  • Protein Folding
  • Protein Multimerization*
  • Protein Structure, Quaternary
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism

Substances

  • ARP7 protein, S cerevisiae
  • ARP9 protein, S cerevisiae
  • Carrier Proteins
  • Chromosomal Proteins, Non-Histone
  • Nucleosomes
  • Rtt102 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Adenosine Triphosphate