Poster Presentation 50th Lorne Proteins Conference 2025

Structural characterisation of the interactions between the SIN3 PAH domains and their binding partners (#107)

Bhagya Mendis 1 2 , Ahmad Wardak 1 , Sean Smyth 1 , Hai Vu Nguyen 1 2 , Suzanne Cory 1 2 , Peter Czabotar 1 2 , Michelle Miller 1 2
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia

Transcriptional repression is critical in eukaryotic cells to downregulate pro-proliferative cell-cycle genes, and initiate cell cycle arrest.1 The corepressor SIN3 acts as a scaffolding protein which forms a complex with histone deacetylases (HDACs) which deacetylate lysine residues on histone H3.2,3 Mammals have two isoforms of SIN3: SIN3A and SIN3B, which assemble into two different, non-redundant repressor complexes.2,3 Both SIN3A and SIN3B complexes regulate the proliferative potential and differentiation of cancer cells.3 To repress transcription, these SIN3 complexes must be recruited by various transcription factors such as MNT and MXD1 through binding to SIN3’s paired amphipathic helix (PAH) domains.4,5 Each SIN3 isoform has three PAH domains (PAH1, PAH2 and PAH3).3 Understanding the interactions between these PAH domains and their binders would provide more insight into the role of these interactions in a cancer setting. To do this, we have employed surface plasmon resonance (SPR) to assess the kinetics, binding affinities and relative specificities of each PAH domains and a series of known interaction partners.

 

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  3. Wan M S M, Muhammad R, Koliopoulos M G, Roumeliotis T I, Choudhary J S and Alfieri C (2023) “Mechanism of assembly, activation
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  5. Yang G and Hurlin P J (2017) “MNT and emerging concepts of MNT-MYC antagonism”, Genes (Basel), 8:83.