RuvBL1 and RuvBL2 and Their Complex Proteins Implicated in Many Cellular Pathways

  • Sabine Gorynia
  • Tiago M. Bandeiras
  • Pedro M. Matias
  • Filipa G. Pinho
  • Colin E. McVey
  • Peter Donner
  • Maria Arménia Carrondo
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)

Abstract

RuvBL1 and its homolog RuvBL2 belong to the AAA+ family of ATPases and play important roles in chromatin remodeling, in transcriptional regulation, in DNA repair and in the c-Myc and Wnt signaling pathways. Proteins involved in these pathways are often mutated in human cancers. Both RuvBL proteins form a complex and act alone or together in diverse cellular processes. The three-dimensional structures of human RuvBL1 refined using diffraction data to 2.2 Å resolution and of the human RuvBL1/RuvBL2 complex with a truncated domain II at 3 Å resolution are presented. The dodecameric RuvBL1/RuvBL2 complex structure differs from previously described models. It consists of two heterohexameric rings with alternating RuvBL1 and RuvBL2 monomers that interact with each other via domain II. ATPase and helicase activities of RuvBL1 and RuvBL2 were also tested. Interestingly, truncation of domain II resulted not only in a substantial increase of ATP consumption by the RuvBL proteins, but also in stimulation of helicase activity, which was not observed with the full-length proteins.

Keywords

AAA+ proteins Helicase X-ray crystallography Chromatin remodeling Transcriptional regulation 

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Sabine Gorynia
    • 1
    • 2
    • 3
  • Tiago M. Bandeiras
    • 4
  • Pedro M. Matias
    • 1
  • Filipa G. Pinho
    • 4
  • Colin E. McVey
    • 1
  • Peter Donner
    • 1
  • Maria Arménia Carrondo
    • 1
  1. 1.Instituto de Tecnologia Química e BiológicaUniversidade Nova de LisboaOeirasPortugal
  2. 2.Lead Discovery Berlin – Protein SupplyBayer Schering Pharma AGBerlinGermany
  3. 3.Department of Biological Chemistry, David Geffen School of MedicineUCLALos AngelesUSA
  4. 4.Instituto de Biologia Experimental e TecnológicaOeirasPortugal

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