Oral Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Architecture of the Nucleosome Remodeling and Deacetylase (NuRD) complex deduced from integrative structural biology (#33)

Jason K.K. Low 1 , Ana P.G. Silva 1 , Medhi Sharifi Tabar 1 , Mario Torrado del Rey 1 , Jason Schmidberger 1 , Sarah Webb 1 , Benjamin Parker 1 , Bishnu Paudel 2 , Antoine van Oijen 2 , Michael Landsberg 3 , Nicholas E Shepherd 1 , Joel Mackay 1
  1. University of Sydney, Camperdown, NSW, Australia
  2. School of Chemistry, University of Wollongong, Wollongong, NSW, Australia
  3. University of Queensland, Brisbane, QLD, Australia

The Nucleosome Remodeling and Deacetylase (NuRD) complex is a ~1-MDa 10-subunit transcriptional co-regulator that plays essential roles in transcriptional regulation and DNA repair in all metazoans. It is also is emerging as a central player in diseases ranging from cancer to thalassemia.

Knowledge of NuRD structure and function will provide broad insight into mechanisms of eukaryotic gene regulation. However, the difficulty of working with this large and dynamic multi-component protein complex has hindered efforts to define its structure and biochemical activity.

To address this deficit, we are using a barrage of biochemical and biophysical approaches to probe the structure of the NuRD complex. We recently showed that the NuRD complex can exist as a separate stable entity in the absence of the remodelling subunit CHD4 — a key result that disrupted the existing paradigm that CHD4 is an integral core component of the complex. We have gone on to deduce the architecture of the complex, interrogating a number of recombinantly expressed subcomplexes by mass spectrometry and single particle electron microscopy. Integration of these diverse data is providing the first glimpses of the structure of this elusive but essential protein complex.